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Computer modeling of prostate biopsy: tumor size and location--not clinical significance--determine cancer detection.

PURPOSE: Sampling error is an inherent problem of prostate biopsy, and the determination of clinical significance based on biopsy results is problematic. We quantify the dimensions of these problems by computer simulation. MATERIALS AND METHODS: We constructed 3-dimensional solid computer models of 59 autopsy prostates containing clinically undetected prostate cancer, and performed simulations of the standard prostate biopsy method. RESULTS: Biopsy simulation detected 19 tumors from the 59 prostates, the majority of which were in the most accessible portion of the prostate, the posterior peripheral zone. Using 0.5 cc or greater tumor volume or less than 0.5 cc and Gleason sum 7 or greater as criteria of significance, the model detected 58% (11 of 19) significant tumors and 20% (8 of 40) insignificant tumors. With 0.25 cc or greater tumor volume or less than 0.25 cc and Gleason sum 7 or greater as criteria 15 of 29 significant (52%) and 4 of 30 insignificant (13%) tumors were detected. Among significant tumors defined by either volume criterion there was a statistical difference between detected and undetected tumors in terms of mean tumor volume and mean ratio of tumor volume-to-prostate volume. Among insignificant tumors defined by either criterion there was no such difference. CONCLUSIONS: As much as 20 to 40% of currently detected prostate cancer may be histologically insignificant, as 4 of 19 cancers were detected when 0.25 cc was used as volume determinant of clinical significance and 8 of 19 were detected when 0.5 cc volume was used. These tumors are detected randomly. On the other hand, perhaps only one-half to three-fourths of clinically significant prostate cancers are being detected, and then only because the volume and anatomic location make them hard to miss.

Adult↗

Multivariate distributions of clinical covariates at the time of cancer detection.

Many screening trials conducted in the past have generated a wealth of interesting data. These data represent an invaluable source of information for furthering our knowledge about the natural history of the disease. The traditional approach to modeling cancer screening tends to describe the process of tumor development in only one dimension, that is, the time natural history. A broader methodological idea is to construct a stochastic model of cancer development and detection that yields the multivariate distribution of observable variables at the time of diagnosis. By focusing on such multivariate observations, rather than just on the age of patients at diagnosis, this idea seeks to invoke an additional source of information (available only at the time of detection) in order to improve an estimation of unobservable quantitative parameters of cancer latency. In this article, we discuss modeling techniques that make the above-mentioned problems approachable. A special focus is placed on analytical tools for deriving joint distributions of clinical covariates at the time of cancer detection under an arbitrary screening protocol. In addition, some future research avenues and public health implications of the proposed approach are discussed.

Aged↗

Relationships of DNA ploidy, S-phase fraction and hormone receptor status to tumor stage in breast cancers detected by population screening. The South-East Sweden Breast Cancer Group.

Cellular DNA content was analyzed by flow cytometry and estrogen and progesterone receptors by an immuno-biochemical method (EIA) in a consecutive series of 807 frozen breast-cancer samples. Before the beginning of the study, a mammography screening program had been introduced in the region where the tumors were diagnosed. Forty percent of the tumors were judged as DNA diploid, of which 86% were ER-positive. The proportion of ER-positive tumors among non-diploids was significantly lower, or 73% (p less than 0.001). S-phase fraction (SPF) was estimated in 691 cases (86%), with an overall mean of 8.4%. DNA ploidy as well as ER and PR status were independently related to SPF. Unlike the results obtained in most older series, the biological variables correlated significantly with tumor staging factors such as lymph-node status and tumor size. Patients with nodal involvement, especially those with 4 positive nodes or more, more often had tumors which were receptor-negative, DNA aneuploid and of high S-phase rate. Large tumor size was significantly related to lower frequencies of receptor positivity and strongly related to DNA aneuploidy and high S-phase fraction. Multiple linear regression analysis showed that these relationships were mainly due to the associations of SPF with the other variables. S-phase fraction was the only independent factor predicting nodal status, while DNA ploidy in addition to SPF was associated with tumor size. In fact, DNA ploidy (p less than 0.001), ER and PR status (p less than 0.001, p = 0.002), nodal status (p = 0.04) and tumor size (p less than 0.001) were all independently related to SPF.

Breast Neoplasms↗

Mammotome: less invasive than ABBI with similar accuracy for early breast cancer detection.

We performed a prospective analysis of two consecutive biopsy cohorts investigated by the same team to compare the Mammotome system with the ABBI procedure. From April 1997 to August 2003 a series of 413 nonpalpable mammographic lesions in 387 women (median age 56 years, range 30-84 years) were stereotactically biopsied in the University Hospital of Basel, Switzerland. Until October 1999 the ABBI system was applied exclusively, it was subsequently superseded by the Mammotome device in our clinic. Main outcome measures were accuracy, technical demand, and morbidity. Sensitivity (97.3%/96.8%), negative predictive value (99.2%/98.7%), and diagnostic accuracy (99.4%/99.1%) regarding the detection of malignancy were excellent for both techniques (ABBI/ Mammotome). The Mammotome procedure was faster and less invasive, thus causing significantly less morbidity. The larger specimen obtained by the ABBI procedure resulted in more detailed histology. In conclusion, recommend the Mammotome system as the method of choice for detecting nonpalpable early breast cancer.

Adult↗

Breast cancer detection based on incremental biochemical and physiological properties of breast cancers: a six-year, two-site study.

RATIONALE AND OBJECTIVES: To demonstrate that near-infrared spectroscopy would achieve sufficient sensitivity and specificity in human breast cancer to reach ROC/AUC values in the 90s and yet to warn of the potential liabilities of introduction of a novel technology in this field. MATERIALS AND METHODS: 116 subjects from two nations (44 were cancer-verified by biopsy and histopathology) were reviewed. NIR spectroscopy of total hemoglobin and its relative oxygenation were monitored in breast cancers and compared to their contralateral breast in a 2D nomogram for diagnostic evaluation. A novel handheld NIR breast cancer detector pad with a 3-wavelength LED and 8 detectors with 4 cm separation between source and detectors was placed on the subject's breast. The method is convenient, rapid, and safe and has achieved high patient compliance with minimal patient apprehension of compression, confinement, or radioactivity. RESULTS: The absorbance increments of the cancerous region are referred to the mirror image location on the contralateral breast. The two metrics are increased hemoglobin concentration due to angiogenesis and decreased hemoglobin saturation due to hypermetabolism of the cancer. The 2D nomogram display of these two metrics shows Zone 1 contains verified cancers and Zone 2 contains noncancers. ROC evaluation of the nomogram gives 95% AUC for the two sites, Philadelphia and Leipzig. CONCLUSION: A simple, economical breast cancer detector has achieved high patient compliance and a high ROC/AUC score for a population which involved a range of tumors down to and including those of 0.8-1 cm in diameter.

Area Under Curve↗

Serum protein expression profiling for cancer detection: validation of a SELDI-based approach for prostate cancer.

Multiple studies have reported that analysis of serum and other bodily fluids using surface enhanced laser desorption/ionization time of flight mass spectroscopy (SELDI-TOF-MS) can identify a "fingerprint" or "signature" of spectral peaks that can separate patients with a specific disease from normal control patients. Ultimately, classification by SELDI-TOF-MS relies on spectral differences in position and amplitude of resolved peaks. Since the reproducibility of quantitation, resolution and mass accuracy of the SELDI-TOF-MS, or any high throughput mass spectrometric technique, has never been determined this method has come under some skepticism as to its clinical usefulness. This manuscript describes a detailed design of a three-phase study to validate the clinical usefulness of SELDI-TOF-MS in the identification of patients with prostatic adenocarcinoma (PCA). At the end of this validation study, the usefulness of the general SELDI-TOF-MS approach to identifying patients with PCA will be demonstrated and how it compares with PCA diagnosis by measuring prostate specific antigen.

Adenocarcinoma↗

Lasers in cancer detection and diagnosis research: enabling characteristics with illustrative examples.

The salient properties of laser light and the way light interacts with biological tissues and molecular constituents of tissues offer possibilities for detection and diagnosis of cancer. In particular, the wavelength selectivity of tunable lasers, narrow bandwidth around the selected wavelength, and spectral brightness enable probing of key molecular constituents of tissues, and endow laser-based techniques with much desired diagnostic potential. This article presents an overview of some recent developments in optical imaging and optical biopsy of different types of cancers, and illustrates the diagnostic role of the color of light.

Biopsy↗

Integrated endoscopy system for simultaneous imaging and spectroscopy for early lung cancer detection.

An integrated endoscopy system for simultaneous imaging and spectroscopy was developed to facilitate more accurate and convenient detection of early lung cancers. A specially designed three-CCD camera in combination with a dedicated light source permits capture of both white-light color images and tissue autofluorescence images without the need to switch between two different cameras. A mirror with an optical fiber at its center, placed at an interim imaging plane inside the camera unit, facilitates simultaneous imaging and spectroscopy measurements in either white-light reflectance mode or fluorescence mode. The system has been successfully tested in a clinic, demonstrating a practical approach to improve both diagnostic sensitivity and specificity at the same time.

Early Diagnosis↗

Quantification of 5-aminolevulinic acid induced fluorescence improves the specificity of bladder cancer detection.

PURPOSE: 5-Aminolevulinic acid induced fluorescence endoscopy has outstanding sensitivity for detecting early stage bladder cancer. Nevertheless, a third of the lesions that show specific fluorescence are histologically benign. We decreased the false-positive rate of 5-aminolevulinic acid induced fluorescence endoscopy by incorporating protoporphyrin IX fluorescence quantification into the standard cystoscopy procedure. MATERIALS AND METHODS: In 25 cases (53 biopsies) of a history of or suspicion for bladder cancer 5-aminolevulinic acid induced fluorescence endoscopy and fluorescence image quantification were performed. For fluorescence image quantification images obtained with a target integrating color charge-coupled device camera were digitized and stored in a personal computer. Red-to-blue ratios were calculated from fluorescence positive lesions and results were correlated with hematoxylin and eosin histology. RESULTS: Malignant fluorescence positive lesions showed significantly stronger fluorescence intensity than fluorescing lesions with benign histology. A threshold was established that decreased the false-positive rate by 30% without affecting sensitivity. CONCLUSIONS: Fluorescence image quantification is a new endoscopic method for objectively selecting multicolor fluorescence bladder lesion images for biopsy. It has the potential of eliminating human error by different surgeons with variable experience in fluorescence endoscopy.

Adult↗