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1. WO2020161028 - IDENTIFICATION DE LA RÉPONSE À UNE RADIO-IMMUNO-THÉRAPIE COMBINÉE

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CLAIMS:

1. A computer-implemented method (200) for identifying responsiveness to therapy for a subject suffering from cancer, the method comprising:

receiving data (202) associated with a cancerous lesion in the subject;

processing the data (204) to determine values for biomarkers in the cancerous lesion; wherein the biomarkers comprise:

(i) an expression level of three prime repair exonuclease 1 (TREX1) in the cancerous lesion;

(ii) an expression level of programmed death-ligand 1 (PD-L1) on tumor cells in the cancerous lesion; and

(iii) a level of infiltration of immune cells in the cancerous lesion;

processing the determined values (206) of the biomarkers by comparing them to a control value to obtain a score indicative of responsiveness of the cancerous lesion to each of a plurality of treatment modalities; wherein the treatment modalities comprise a defined radiation dose and/or fractionation in combination with immunotherapy;

ranking the treatment modalities (208) based on the obtained responsiveness scores in order to indicate a treatment modality that is likely to be most effective in treating the cancerous lesion in the subject;

providing output comprising the ranking for the treatment modalities to a user on a display for decision support for choosing the treatment modality for the cancerous lesion.

2. A method according to claim 1, wherein the method comprises receiving data associated with a plurality of different cancerous lesions in the subject; processing the data to determine values for the biomarkers in each cancerous lesion; and processing the values of the biomarkers to obtain a score indicative of responsiveness of each cancerous lesion in the subject to the treatment modalities.

3. A method according to claim 2, further comprising ranking each lesion based on the obtained scores, thereby indicating a lesion in the subject to be selected for

radiotherapy and immunotherapy combination treatment.

4. A method according to any preceding claim, wherein an increased value of the expression level of TREX1 in the cancerous lesion compared to a control value is processed to obtain a score indicative of reduced responsiveness of the lesion to radiotherapy and immunotherapy combination treatment, compared to immunotherapy alone.

5. A method according to any preceding claim, wherein a reduced or unchanged value of the expression level of TREX1 in the cancerous lesion compared to the control value is processed to obtain a score indicative of increased responsiveness of the lesion to hypofractionated radiotherapy and immunotherapy combination treatment, compared to standard or single dose radiotherapy and immunotherapy combination treatment.

6. A method according to any preceding claim, wherein an increased value of the expression level of PD-L1 on tumor cells and/or a reduced level of infiltration of immune cells in the cancerous lesion compared to a control value is processed to obtain a score indicative of reduced responsiveness of the lesion to radiotherapy and immunotherapy combination treatment, compared to a lesion showing a lower value of the expression level of PD-L1 on tumor cells and/or an increased level of infiltration of immune cells.

7. A method according to any preceding claim, further comprising calculating an expected volume change of the cancerous lesion in response to the one or more treatment modalities.

8. A method according to any preceding claim, wherein the received data is derived from RNA sequencing, polymerase chain reaction (PCR), microarray analysis or immunohistochemistry of biopsy sample obtained from the subject.

9. A method according to any preceding claim, wherein the immune cells comprise tumour infiltrating lymphocytes.

10. A method according to claim 9, wherein the tumour infiltrating lymphocytes are CD8+, CD4+, FOXP3+ and/or CD3+ T cells.

11. A method according to any preceding claim, wherein the immunotherapy comprises treatment with one or more immune checkpoint inhibitors.

12. A method according to any preceding claim, the received data is derived from positron emission tomography (PET) imaging of one or more of the biomarkers in the subject.

13. A method according to any preceding claim, wherein the treatment modalities are stored in a treatment plan database; one or more treatment modalities are extracted from the database for analysis; each extracted treatment modality is analysed to determine a score indicative of responsiveness of the cancerous lesion to the treatment modality; and a treatment modality having a score indicative highest responsiveness is indicated to be selected for treatment of the subject.

14. A system (100) for identifying responsiveness to therapy for a subject suffering from cancer, the system comprising:

an interface (110) for receiving data associated with a cancerous lesion in the subject;

a memory (106); and

a processor (104) configured to execute instructions stored on the memory to:

(a) process the data to determine values for biomarkers in the cancerous lesion; wherein the biomarkers comprise:

i) an expression level of three prime repair exonuclease 1 (TREX1) in the cancerous lesion;

(ii) an expression level of programmed death-ligand 1 (PD-L1) on tumor cells in the cancerous lesion; and

(iii) a level of infiltration of immune cells in the cancerous lesion; and

(b) process the determined values of the biomarkers by comparing them to a control value to obtain a score indicative of responsiveness of the cancerous lesion to each of al plurality of treatment modalities; wherein the treatment modalities comprise a defined radiation dose and/or fractionation in combination with immunotherapy;

(c) rank the treatment modalities based on the obtained responsiveness scores in order to indicate a treatment modality that is likely to be most effective in treating the cancerous lesion in the subject; and

the system further comprising a display for providing output to a user, the output comprising the ranking for the treatment modalities for decision support for choosing the treatment modality for the cancerous lesion.

15. A computer program product comprising a non-transitory computer readable medium, the computer readable medium having computer readable code embodied therein, the computer readable code being configured such that, on execution by a suitable computer or processor, the computer or processor is caused to perform the method of any of claims 1 to 13.