Methods and apparatuses for predicting risk of prostate cancer and prostate gland volume

Patent metadata

Field	Value
Publication number	US-9672329-B2
Application number	US-201313785058-A
Country	US
Kind code	B2
Filing date	Mar 5, 2013
Priority date	Mar 5, 2012
Publication date	Jun 6, 2017
Grant date	Jun 6, 2017

Abstract

Methods and apparatuses for predicting risk of prostate cancer and/or prostate gland volume are provided. More particularly, this disclosure relates to methods and apparatuses for providing the models and employing the models for predicting risk of prostate cancer and/or predicting prostate gland volume. The methods and apparatuses for predicting risk of prostate cancer and/or prostate gland volume are provided using, at least in part, information from a panel of kallikrein markers.

First claim

The invention claimed is:

1. An assay system comprising:
an analysis region comprising one or more binding partners immobilized to a solid phase portion therein, wherein the one or more binding partners are selected from a group consisting of binding partners that bind total prostate-specific antigen (tPSA), binding partners that bind free prostate-specific antigen (fPSA), binding partners that bind intact prostate-specific antigen (iPSA) and binding partners that bind human kallikrein 2 (hK2);
a detection device, the detection device being configured to detect a presence of an analyte in a sample from the analysis region, wherein the analyte is selected from a group consisting of tPSA, fPSA, iPSA, and hK2; and
a computer programmed to:
process information determined by the detection device indicative of the presence of the analyte, wherein the information includes information for fPSA and tPSA, wherein processing the information determined by the detection device comprises:
defining a first cubic spline and a second cubic spline for tPSA, wherein each of the first cubic spline and the second cubic spline is defined using a first internal knot between 2-5 and a second internal knot between 5-8;
defining a third cubic spline and a fourth cubic spline for fPSA, wherein each of the third cubic spline and fourth cubic spline is defined using a third internal knot between 0.25-1 and a fourth internal knot between 1.0-2.0;
calculating a first tPSA value by evaluating the first cubic spline using the received tPSA value;
calculating a second tPSA value by evaluating the second cubic spline using the received tPSA value;
calculating a first fPSA value by evaluating the third cubic spline using the received fPSA value;
calculating a second fPSA value by evaluating the fourth cubic spline using the received fPSA value;
evaluating a logistic regression model that includes the first tPSA value, the second tPSA value, the first fPSA value, and the second fPSA value to determine a logit;
determining a probability of an event associated with prostate cancer based, at least in part, on the logit; and
outputting an indication of the probability of the event associated with prostate cancer.

2. The assay system of claim 1 , wherein evaluating a logistic regression model comprises scaling the first tPSA value by a first coefficient and scaling the second tPSA value by a second coefficient value to produce scaled tPSA values and summing the scaled tPSA values; and
wherein evaluating a logistic regression model further comprises scaling the first fPSA value by a third coefficient and scaling second fPSA value by a fourth coefficient to produce scaled fPSA values and summing the scaled fPSA values.

3. The assay system of claim 1 , wherein the input includes information for iPSA and hK2, and wherein evaluating the logistic regression model further includes terms based, at least in part, on the information for iPSA, and the information for hK2.

4. The assay system of claim 1 , wherein the first internal knot is specified as 3.89, the second internal knot is specified as 5.54, the third internal knot is specified as 0.81, and the fourth internal knot is specified as 1.19.

5. The assay system of claim 1 , wherein outputting an indication of the probability of the event associated with prostate cancer comprises outputting an indication of an estimated prostate gland volume.

6. The assay system of claim 1 , wherein outputting an indication of the probability of the event associated with prostate cancer comprises outputting an indication of a likelihood that a prostate cancer biopsy will be positive.

7. The assay system of claim 1 , wherein the detection device utilizes an optical or luminescent detection technique selected from the group consisting of light transmission, light absorbance, light scattering, light reflection, visual techniques, photoluminescence, fluorescence, chemiluminescence, bioluminescence, and electrochemiluminescence.

8. The assay system of claim 1 , wherein the detection device detects chemiluminescent or fluorescent emissions, and wherein the chemiluminescent or fluorescent emissions are indicative of an analyte bound to the analyte binding partner.

9. The assay system of claim 1 , wherein the detection device detects variation of a light signal as a function of time.

10. The assay system of claim 1 , wherein the sample is whole blood, serum, or plasma.

11. The assay system of claim 1 , wherein the analysis region comprises a microfluidic channel including at least one inlet and one outlet.

12. A method, comprising:
detecting, by a detection device, a presence of an analyte in a sample from an analysis region of an assay system comprising one or more binding partners immobilized to a solid phase portion therein, wherein the one or more binding partners are selected from a group consisting of binding partners that bind total prostate-specific antigen (tPSA), binding partners that bind free prostate-specific antigen (fPSA), binding partners that bind intact prostate-specific antigen (iPSA) and binding partners that bind human kallikrein 2 (hK2), wherein the analyte is selected from a group consisting of tPSA, fPSA, iPSA, and hK2;
processing, by at least one computer processor, information determined by the detection device indicative of the presence of the analyte, wherein the input includes information for fPSA and tPSA, and wherein processing the information determined by the detection device comprises:
defining, by the at least one computer processor, a first cubic spline and a second cubic spline for tPSA, wherein each of the first cubic spline and the second cubic spline is defined using a first internal knot between 2-5 and a second internal knot between 5-8;
defining, by the at least one computer processor, a third cubic spline and a fourth cubic spline for fPSA, wherein each of the third cubic spline and fourth cubic spline is defined using a third internal knot between 0.25-1 and a fourth internal knot between 1.0-2.0;
calculating, by the at least one computer processor, a first tPSA value by evaluating the first cubic spline using the received tPSA value;
calculating, by the at least one computer processor, a second tPSA value by evaluating the second cubic spline using the received tPSA value;
calculating, by the at least one computer processor, a first fPSA value by evaluating the third cubic spline using the received fPSA value;
calculating, by the at least one computer processor, a second fPSA value by evaluating the fourth cubic spline using the received fPSA value;
evaluating, by the at least one computer processor, a logistic regression model that includes the first tPSA value, the second tPSA value, the first fPSA value, and the second fPSA value to determine a logit;
determining, by the at least one computer processor, a probability of an event associated with prostate cancer based, at least in part, on the logit; and
outputting an indication of the probability of the event associated with prostate cancer.

13. A non-transitory computer-readable storage medium encoded with a plurality of instructions that, when executed by a computer, perform a method, wherein the method comprises:
detecting, by a detection device, a presence of an analyte in a sample from an analysis region of an assay system comprising one or more binding partners immobilized to a solid phase portion therein, wherein the one or more binding partners are selected from a group consisting of binding partners that bind total prostate-specific antigen (tPSA), binding partners that bind free prostate-specific antigen (fPSA), binding partners that bind intact p

Assignees

• Oy Arctic Partners Ab
• Opko Diagnostics Llc

Inventors

• Vickers Andrew J
• Scardino Peter T
• Lilja Hans
• Linder Vincent
• Steinmiller David

Classifications

• G01N33/57555

  of the prostate · CPC title

• B01L2300/0654

  Lenses; Optical fibres · CPC title

• G16H10/40

  for data related to laboratory analysis, e.g. patient specimen analysis · CPC title

• B01L3/502715

  characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces · CPC title

• B01L2300/087

  Multiple sequential chambers · CPC title