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PubMed1995

Esophageal carcinoma metastatic to the brain: clinical value and cost-effectiveness of routine enhanced head CT before esophagectomy.

PURPOSE: To assess the value of screening enhanced head CT before esophagectomy for carcinoma, identify increased risk factor(s) for brain metastases, and determine metastasis incidence. METHODS: Thoracic surgery files of patients undergoing esophagectomies for squamous carcinomas, adenocarcinomas, and undifferentiated carcinomas between January 1984 and March 1993 were reviewed regarding sex, size (length) of neoplasm, and brain metastases. Surgical pathology and tumor registry files also were reviewed. Records of patients with brain metastases were reviewed in detail. RESULTS: Three hundred thirty-four esophagectomies were performed for 230 adenocarcinomas (202 male, 28 female) and 104 squamous carcinomas (61 male, 43 female). In 9 males and 1 female with adenocarcinomas and 1 male and 1 female with squamous carcinomas, brain metastases developed. Surgical pathology files identified 293 additional esophageal carcinomas, including 2 males with adenocarcinomas metastatic to brain. Tumor registry files identified I additional male with brain metastasis from an undifferentiated esophageal neoplasm. No statistically significant preoperative characteristic of esophageal carcinomas with proneness to brain metastases was found, except large size of primary neoplasm. Preoperative screening head CT done on approximately 240 patients who underwent esophagectomies showed no metastases. CONCLUSIONS: Brain metastases from carcinomas of the esophagus are relatively uncommon (3.6% in the esophagectomy cohort). They tend to occur in patients with large primary neoplasm, probably especially adenocarcinomas involving the esophagogastric junction, and with findings of local invasion and lymph node metastases by CT and/or microscopically. It may be reasonable to obtain head CT as a last preoperative staging procedure in such patients. Routine preoperative head CT for staging is not cost effective.

Aged↗
PubMed2005

Analysis of time-dependent covariates in a regressive relative survival model.

Relative survival is a method for assessing prognostic factors for disease-specific mortality. However, most relative survival models assume that the effect of covariate on disease-specific mortality is fixed-in-time, which may not hold in some studies and requires adapted modelling. We propose an extension of the Esteve et al. regressive relative survival model that uses the counting process approach to accommodate time-dependent effect of a predictor's on disease-specific mortality. This approach had shown its robustness, and the properties of the counting process give a simple and attractive computational solution to model time-dependent covariates. Our approach is illustrated with the data from the Stanford Heart Transplant Study and with data from a hospital-based study on invasive breast cancer. Advantages of modelling time-dependent covariates in relative survival analysis are discussed.

Adult↗
PubMed1999

Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population.

In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age +/- SD was 46 +/- 11.6 years which is distinctly different from the 60-65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage IIIA and Stage III B. Patients received multimodality treatment, including surgery, adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95% CI, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% CI, 14.2 to 113 months). Cox proportional hazard model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III B disease (as compared with Stage III A) and axillary nodal status was evident. Whilst the favourable effect of radiotherapy on survival was demonstrated, the lack of independent efficacy of other modalities (adjuvant chemotherapy and tamoxifen) or the apparent deleterious effect of neoadjuvant chemotherapy should be addressed with discretion in such retrospective analysis. Optimal management of patients with locally advanced breast cancer disease should be appraised in well designed, prospective, randomised studies.

Adult↗
PubMed2003

Assessment of clinical utility of 18F-FDG PET in patients with head and neck cancer: a probability analysis.

The purpose of this study was to calculate disease probabilities based on data of patients with head and neck cancer in the register of our institution and to perform a systematic review of the available data on the accuracy of PET in the primary assessment and follow-up of patients with head and neck cancer. The pre-test probability of head and neck cancer among patients in our institutional data registry was assessed. Then the published literature was selected and appraised according to a standard protocol of systematic reviews. Two reviewers independently selected and extracted data on study characteristics, quality and accuracy. Accuracy data were used to form 2 x 2 contingency tables and were pooled to produce summary receiver operating characteristic (ROC) curves and summary likelihood ratios for positive and negative testing. Finally post-test probabilities were calculated on the basis of the pre-test probabilities of this patient group. All patients had cytologically or histologically proven cancer. The prevalence of additional lymph node metastases on PET in staging examinations was 19.6% (11/56), and that of locoregional recurrence on restaging PET was 28.6% (12/42). In the primary assessment of patients, PET had positive and negative likelihood ratios of 3.9 (2.56-5.93) and 0.24 (0.14-0.41), respectively. Disease probabilities were therefore 49.4% for a positive test result and 5.7% for a negative test result. In the assessment of recurrence these values were 3.96 (2.8-5.6) and 0.16 (0.1-0.25), resulting in probabilities of 49.7% and 3.8%. PET evaluation for involvement of lymph nodes had positive and negative likelihood ratios of 17.26 (10.9-27.3) and 0.19 (0.13-0.27) for primary assessment and 11.0 (2.93-41.24) and 0.14 (0.01-1.88) for detection of recurrence. The probabilities were 81.2% and 4.5% for primary assessment and 73.3% and 3.4% for assessment of recurrence. It is concluded that in this clinical setting the main advantage of PET is the ability to reliably rule out the presence of disease in both staging and restaging. Further research is required to derive probabilities for individual patients from sequential testing as applied in the diagnostic work-up of patients with head and neck cancer.

Adult↗
PubMed2004

Gene selection and classification from microarray data using kernel machine.

The discrimination of cancer patients (including subtypes) based on gene expression data is a critical problem with clinical ramifications. Central to solving this problem is the issue of how to extract the most relevant genes from the several thousand genes on a typical microarray. Here, we propose a methodology that can effectively select an informative subset of genes and classify the subtypes (or patients) of disease using the selected genes. We employ a kernel machine, kernel Fisher discriminant analysis (KFDA), for discrimination and use the derivatives of the kernel function to perform gene selection. Using a modified form of KFDA in the minimum squared error (MSE) sense and the gradients of the kernel functions, we construct an effective gene selection criterion. We assess the performance of the proposed methodology by applying it to three gene expression datasets: leukemia dataset, breast cancer dataset and colon cancer dataset. Using a few informative genes, the proposed method accurately and reliably classified cancer subtypes (or patients). Also, through a comparison study, we verify the reliability of the gene selection and discrimination results.

Algorithms↗
PubMed2004

A four-dimensional simulation model of tumour response to radiotherapy in vivo: parametric validation considering radiosensitivity, genetic profile and fractionation.

The aim of this paper is to present the current state of a four-dimensional simulation model of solid tumour growth and response to radiotherapy developed by our group. The most prominent points of the algorithms describing the fundamental biological phenomena involved are outlined. A specific application of the model to a selected clinical case of glioblastoma multiforme is described and comparative studies are performed, using various exploratory values of the model parameters. Qualitative agreement with clinical observations has been achieved. Special emphasis is laid on the variability of radiosensitivity parameters throughout the cell cycle and on the influence of the genetic profile of the tumour on its radiosensitivity. The results of the simulation are three-dimensionally reconstructed. A valuable tool for getting insight into the biology of tumour growth and response to radiotherapy and at the same time an advanced patient specific decision support system is expected to emerge after the completion of the necessary extensive clinical evaluation.

Brain Neoplasms↗
PubMed2006

Established breast cancer risk factors by clinically important tumour characteristics.

Breast cancer is a morphologically and clinically heterogeneous disease; however, it is less clear how risk factors relate to tumour features. We evaluated risk factors by tumour characteristics (histopathologic type, grade, size, and nodal status) in a population-based case-control of 2386 breast cancers and 2502 controls in Poland. Use of a novel extension of the polytomous logistic regression permitted simultaneous modelling of multiple tumour characteristics. Late age at first full-term birth was associated with increased risk of large (> 2 cm) tumours (odds ratios (95% confidence intervals) 1.19 (1.07-1.33) for a 5-year increase in age), but not smaller tumours (P for heterogeneity adjusting for other tumour features (Phet) = 0.007). On the other hand, multiparity was associated with reduced risk for small tumours (0.76 (0.68-0.86) per additional birth; Phet = 0.004). Consideration of all tumour characteristics simultaneously revealed that current or recent use of combined hormone replacement therapy was associated with risk of small (2.29 (1.66-3.15)) and grade 1 (3.36 (2.22-5.08)) tumours (Phet = 0.05 for size and 0.0008 for grade 1 vs 3), rather than specific histopathologic types (Phet = 0.63 for ductal vs lobular). Finally, elevated body mass index was associated with larger tumour size among both pre- and postmenopausal women (Phet = 0.05 and 0.0001, respectively). None of these relationships were explained by hormone receptor status of the tumours. In conclusion, these data support distinctive risk factor relationships by tumour characteristics of prognostic relevance. These findings might be useful in developing targeted prevention efforts.

Breast Neoplasms↗
PubMed1998

Population pharmacokinetic parameters of gentamicin in patients with solid tumors: estimation by one- and two-stage methods.

Gentamicin monitoring has been improved with the introduction of Bayesian methods but the usefulness depends on the quality of the population parameters (PP) used. The objective of this study was to determine PP of gentamicin in patients with solid tumors. A total of 198 adult patients with cancer were included in the analysis. Population parameters were estimated by both a two-stage and a one-stage method (NPEM, Non Parametric Expectation Maximization). Individual parameters (IP) were estimated by the Sawchuk-Zaske method and by nonlinear regression. The estimated distribution volume and clearance of gentamicin (mean +/- SD) were 18.37 +/- 5.021 (0.30-0.32 l/kg of dosing weight) and 3.34 +/- 1.6 l/h, respectively. No significant differences between IP or PP obtained by the different methods were found. The results indicated a wide variability of gentamicin pharmacokinetics making monitoring necessary and that patients with solid tumors may have larger gentamicin volume and slower clearance than normal patients. These observations imply that different population pharmacokinetic parameters should be used for this group of patients.

Adult↗
PubMedDate not supplied

Tumor size and lymph node status in multifocal breast cancer.

Tumor size correlates with lymph node metastasis in breast cancer. In multifocal lesions there is controversy about considering the summation of the largest diameter of each tumor. A total of 122 patients with multifocal breast cancer were compared in a retrospective study with 177 patients with unifocal tumors, correlating tumor size with lymph node metastasis. In multifocal tumors, two sizes were considered: the diameter of the largest tumor and the combined diameter of all lesions. Relationship was established by three different logistic models using variables such as age, number of lesions, histologic type, and grade. At a same size of the largest diameter of a unifocal or multifocal lesions and the combined diameter of a multifocal lesion, the latter shows less probability of nodal metastasis indicating that combined diameter is an overestimation of the lesion size. Our results indicate that in multifocal breast cancer, only the diameter of the largest tumor breast cancer has relationship with lymph node metastasis.

Adult↗