IP Library Granted Patent US 12,224,043
Granted Patent B2
US 12,224,043 · App. 18/367,923 · Granted Feb 11, 2025

Methods for determining treatment for cancer patients

Inventors: Li Yu (Gaithersburg, MD); Harry Yang (Gaithersburg, MD); Mohammed Dar (Gaithersburg, MD); Lorin Roskos (Gaithersburg, MD); Jean-Charles Soria (Gaithersburg, MD); Charles Ferte (Gaithersburg, MD); Wei Zhao (Gaithersburg, MD); Aline Gendrin Brokmann (Cambridge, GB); Jolyon Faria (Cambridge, GB); Pralay Mukhopadhyay (Wilmington, DE); Ikbel Achour (Gaithersburg, MD)
Assignee: MEDIMMUNE, LLC
G16B40/20G06N5/01G06N20/20G16B5/20G16H50/20G16H50/30G16H50/50A61K38/00C07K16/2818G01N33/57484G16H20/40
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Quick Facts
Patent No.
US 12,224,043
App. No.
18/367,923
Granted
Feb 11, 2025
Kind
B2
Abstract

Methods for determining treatments for cancer patients are disclosed.

Claims (53)

1. A computing system comprising:

computer memory configured to store model training data, wherein the model training data involves a first set of cancer patients that underwent cancer treatments, wherein the model training data associates (i) results from laboratory tests conducted on the first set of cancer patients and tumor types of the first set of cancer patients with (ii) whether individuals from the first set of cancer patients died within a threshold number of weeks from initiation of the cancer treatments; and

one or more processors in communication with the computer memory and configured to execute program instructions to:

generate a plurality of variations of a gradient boosting machine learning model, wherein generating each of the variations comprises:

training, based on the model training data, a sequential series of decision trees until a stopping condition is reached using a respective set of hyperparameters, wherein each subsequent decision tree of the sequential series of decision trees is constructed based on residual values of its preceding decision tree of the sequential series of decision trees, and wherein the respective sets of hyperparameters are different for each of the variations; and

forming an additive function of the sequential series of decision trees, wherein each of the variations of the gradient boosting machine learning model is usable to predict whether a further cancer patient dies within the threshold number of weeks based on the additive function applied to results from the laboratory tests as conducted on the further cancer patient and a tumor type of the further cancer patient;

apply each of the variations of the gradient boosting machine learning model to the model training data; and

select, from among the variations of the gradient boosting machine learning model, a particular variation that provides predictions of whether the first set of cancer patients die within the threshold number of weeks from initiation of the cancer treatments within a threshold degree of accuracy.

2. The computing system of claim 1 , wherein the results from the laboratory tests provide one or more of: a neutrophil to lymphocyte ratio, a neutrophil level, an albumin level, a lactate dehydrogenase level, an aspartate amino transferase level, or a gamma-glutamyl transferase level.

3. The computing system of claim 2 , wherein the neutrophil to lymphocyte ratio, the neutrophil level, the albumin level, the lactate dehydrogenase level, the aspartate amino transferase level, and the gamma-glutamyl transferase level were selected from 20 or more laboratory tests conducted on the first set of cancer patients, wherein the selecting comprises:

training the sequential series of decision trees in each of the plurality of variations of the gradient boosting machine learning model on the 20 or more laboratory tests;

for each respective laboratory test, generating an additional variation of the gradient boosting machine learning model, wherein generating the additional variation of the gradient boosting machine learning model comprises training the sequential series of decision trees on the 20 or more laboratory tests with the respective laboratory test removed; and

determining predictive values of each of the 20 or more laboratory tests by comparing accuracies of the additional variations of the gradient boosting machine learning model.

4. The computing system of claim 1 , wherein the tumor type is one of: non-small cell lung cancer, urothelial carcinoma, squamous cell carcinoma of head and neck, gastric cancer, renal cell carcinoma, or Hodgkin's lymphoma.

5. The computing system of claim 1 , wherein predicting whether the further cancer patient dies within the threshold number of weeks comprises:

determining, using the selected variation of the gradient boosting machine learning model, a probability that the further cancer patient dies within the threshold number of weeks.

6. The computing system of claim 5 , wherein predicting whether the further cancer patient dies within the threshold number of weeks further comprises:

based on the probability and a cutoff value, placing the further cancer patient into either a high risk of death category or a low risk of death category.

7. The computing system of claim 6 , wherein the cutoff value is selected so that there is no more than a false positive rate of 5-20% when predicting whether the first set of cancer patients die within the threshold number of weeks.

8. The computing system of claim 6 , wherein cancer patients placed in the high risk of death category are excluded from a clinical trial for treatment of cancer, and wherein cancer patients placed in the low risk of death category are included in the clinical trial for treatment of cancer.

9. The computing system of claim 1 , wherein the computer memory is further configured to store model tuning data, wherein the model tuning data involves a second set of cancer patients that underwent cancer treatments, wherein the model tuning data associates (i) results from the laboratory tests as conducted on the second set of cancer patients and tumor types of the second set of cancer patients with (ii) whether the second set of cancer patients died within the threshold number of weeks from initiation of the cancer treatments, and

wherein the one or more processors are further configured to execute further program instructions to:

apply each of the variations of the gradient boosting machine learning model to the model tuning data; and

select, from among the variations of the gradient boosting machine learning model, a particular variation that provides predictions of whether the second set of cancer patients die within the threshold number of weeks from initiation of the cancer treatments within the threshold degree of accuracy.

10. The computing system of claim 1 , wherein the hyperparameters include one or more of: maximum depth of the decision trees set to 2, 3, 4, 5, or 6, minimum loss reduction required to split a node in the decision trees set to 0, 1, 2, 3, or 4, minimum sum of weights of all observations required in a child node in the decision trees set between 3.0 and 7.0, fraction of input parameters to be randomly sampled for each of the decision trees set between 0.7 and 1.0, fraction of observations to be randomly sampled for each of the decision trees set between 0.4 and 0.8, number of decision trees in the sequential series of decision trees set between 10 and 25.

11. A computer-implemented method comprising:

obtaining model training data, wherein the model training data involves a first set of cancer patients that underwent cancer treatments, wherein the model training data associates (i) results from laboratory tests conducted on the first set of cancer patients and tumor types of the first set of cancer patients with (ii) whether individuals from the first set of cancer patients died within a threshold number of weeks from initiation of the cancer treatments;

generate a plurality of variations of a gradient boosting machine learning model, wherein generating each of the variations comprises:

training, based on the model training data, a sequential series of decision trees until a stopping condition is reached using a respective set of hyperparameters, wherein each subsequent decision tree of the sequential series of decision trees is constructed based on residual values of its preceding decision tree of the sequential series of decision trees, and wherein the respective sets of hyperparameters are different for each of the variations; and

forming an additive function of the sequential series of decision trees, wherein each of the variations of the gradient boosting machine learning model is usable to predict whether a further cancer patient dies within the threshold number of weeks based on the additive function applied to results from the laboratory tests as conducted on the further cancer patient and a tumor type of the further cancer patient;

applying each of the variations of the gradient boosting machine learning model to the model training data; and

selecting, from among the variations of the gradient boosting machine learning model, a particular variation that provides predictions of whether the first set of cancer patients die within the threshold number of weeks from initiation of the cancer treatments within a threshold degree of accuracy.

12. The computer-implemented method of claim 11 , wherein the results from the laboratory tests provide one or more of: a neutrophil to lymphocyte ratio, a neutrophil level, an albumin level, a lactate dehydrogenase level, an aspartate amino transferase level, or a gamma-glutamyl transferase level.

13. The computer-implemented method of claim 11 , wherein the tumor type is one of: non-small cell lung cancer, urothelial carcinoma, squamous cell carcinoma of head and neck, gastric cancer, renal cell carcinoma, or Hodgkin's lymphoma.

14. A computer-implemented method comprising:

obtaining a gradient boosting machine learning model, wherein the gradient boosting machine learning model was trained on model training data, wherein the model training data involves a first set of cancer patients that underwent cancer treatments, wherein the model training data associates (i) results from laboratory tests conducted on the first set of cancer patients and tumor types of the first set of cancer patients with (ii) whether individuals from the first set of cancer patients died within a threshold number of weeks from initiation of the cancer treatments, wherein training the gradient boosting machine learning model involved:

(i) generating a plurality of variations of a gradient boosting machine learning model, wherein generating each of the variations involved:

training, based on the model training data, a sequential series of decision trees until a stopping condition was reached using a respective set of hyperparameters, wherein each subsequent decision tree of the sequential series of decision trees was constructed based on residual values of its preceding decision tree of the sequential series of decision trees, and wherein the respective sets of hyperparameters are different for each of the variations; and

forming an additive function of the sequential series of decision trees;

(ii) applying each of the variations of the gradient boosting machine learning model to the model training data; and

(iii) selecting, from among the variations of the gradient boosting machine learning model, a particular variation that provides predictions of whether the first set of cancer patients die within the threshold number of weeks from initiation of the cancer treatments within a threshold degree of accuracy;

obtaining results from the laboratory tests as conducted on a further cancer patient;

obtaining a tumor type of the further cancer patient;

applying the gradient boosting machine learning model to results from the laboratory tests as conducted on a further cancer patient and the tumor type of the further cancer patient; and

receiving, from the gradient boosting machine learning model, a prediction of whether the further cancer patient dies within the threshold number of weeks.

15. The computer-implemented method of claim 14 , wherein the results from the laboratory tests provide one or more of: a neutrophil to lymphocyte ratio, a neutrophil level, an albumin level, a lactate dehydrogenase level, an aspartate amino transferase level, or a gamma-glutamyl transferase level.

16. The computer-implemented method of claim 14 , wherein the tumor type is one of: non-small cell lung cancer, urothelial carcinoma, squamous cell carcinoma of head and neck, gastric cancer, renal cell carcinoma, or Hodgkin's lymphoma.

17. The computer-implemented method of claim 14 , wherein predicting whether the further cancer patient dies within the threshold number of weeks comprises:

determining, using the selected variation of the gradient boosting machine learning model, a probability that the further cancer patient dies within the threshold number of weeks.

18. The computer-implemented method of claim 17 , wherein predicting whether the further cancer patient dies within the threshold number of weeks further comprises:

based on the probability and a cutoff value, placing the further cancer patient into either a high risk of death category or a low risk of death category.

19. The computer-implemented method of claim 18 , wherein the cutoff value was selected so that there is no more than a false positive rate of 5-20% when predicting whether the first set of cancer patients die within the threshold number of weeks.

20. The computer-implemented method of claim 18 , wherein cancer patients placed in the high risk of death category are excluded from a clinical trial for treatment of cancer, and wherein cancer patients placed in the low risk of death category are included in the clinical trial for treatment of cancer.

Assignments (11)
CORRECTIVE ASSIGNMENT TO CORRECT THE THE EXECUTION DATE OF THE SECOND INVENTOR PREVIOUSLY RECORDED AT REEL: 65166 FRAME: 582. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded May 13, 2024
From: YU, LI; YANG, HARRY; DAR, MOHAMMED; ROSKOS, LORIN; SORIA, JEAN-CHARLES; FERTE, CHARLES
To: MEDIMMUNE, LLC
Reel/Frame 068916/0818 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 11, 2023
From: ACHOUR, IKBEL
To: MEDIMMUNE, LLC
Reel/Frame 065185/0153 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: ZHAO, WEI
To: MEDIMMUNE, LLC
Reel/Frame 065166/0780 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: ZHAO, WEI
To: MEDIMMUNE, LLC
Reel/Frame 065166/0903 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: GENDRIN BROKMANN, ALINE; FARIA, JOLYON
To: ASTRAZENECA UK LIMITED
Reel/Frame 065167/0150 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: MUKHOPADHYAY, PRALAY
To: ASTRAZENECA PHARMACEUTICALS LP
Reel/Frame 065167/0551 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: ASTRAZENECA PHARMACEUTICALS LP
To: ASTRAZENECA UK LIMITED
Reel/Frame 065168/0831 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: ASTRAZENECA AB
To: MEDIMMUNE, LLC
Reel/Frame 065174/0672 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: ASTRAZENECA UK LIMITED
To: ASTRAZENECA AB
Reel/Frame 065197/0503 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 10, 2023
From: YU, LI; YANG, HARRY; DAR, MOHAMMED; ROSKOS, LORIN; SORIA, JEAN-CHARLES; FERTE, CHARLES
To: MEDIMMUNE, LLC
Reel/Frame 065166/0582 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 9, 2023
From: YU, LI; YANG, HARRY; DAR, MOHAMMED; ROSKOS, LORIN; SORIA, JEAN-CHARLES; FERTE, CHARLES
To: MEDIMMUNE, LLC
Reel/Frame 065162/0430 →
Continuity (4)
Continuation 16657375 · Oct 18, 2019
Provisional Application 62854566 · May 30, 2019
Provisional Application 62747420 · Oct 18, 2018
Related Publication 20230420081A1 · Dec 28, 2023
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