Prognosis evaluation method and system for icis retreatment or rechallenge

Abstract

This invention relates to a method and system for prognostic assessment of ICI retreatment or rechallenge, the system comprising: (1) a storage device storing information including the patient's SII-PNI score before undergoing ICI retreatment or rechallenge; (2) a prediction device that predicts the patient's prognosis and / or treatment efficacy based on the patient's SII-PNI score; and (3) an output device that outputs the predicted prognosis and / or treatment efficacy. The assessment method and system of this invention can conveniently and effectively assess and predict prognosis and / or treatment efficacy, helping physicians and patients decide whether to choose ICI retreatment or rechallenge therapy.

Description

Technical Field

[0001] This invention belongs to the field of prognostic assessment of ICI therapy, specifically involving prognostic assessment methods and systems for ICI retreat or re-challenge. Background Technology

[0002] Lung cancer is a leading cause of cancer death worldwide and the leading cause of both morbidity and mortality in my country. 70% to 80% of lung cancer patients are diagnosed at an advanced stage, missing the optimal treatment window, resulting in a low five-year survival rate and poor prognosis.

[0003] The advent of immune checkpoint inhibitors (ICIs) has opened a new chapter in cancer treatment. However, due to immune-related adverse events (irAEs) or various other reasons, such as disease progression and long-term treatment, patients may discontinue immunotherapy. In such cases, readjusting with ICIs may be an effective strategy. To ensure patients receive the most effective treatment, timely and reliable assessment by clinicians of the clinical benefit and expected survival after restarting ICI therapy in patients with advanced non-small cell lung cancer is crucial. This assessment helps physicians and patients collaboratively select appropriate treatment regimens, thereby achieving personalized care.

[0004] Therefore, a convenient and effective model is needed to assess the prognosis of immune retreat or re-challenge. In view of this, the present invention is proposed. Summary of the Invention

[0005] This invention establishes a method and system for assessing the prognosis or treatment efficacy of non-small cell lung cancer patients undergoing ICIs retreatment or rechallenge by analyzing the correlation between the patient's immune status before receiving immune retreatment or rechallenge and the prognosis of immune retreatment or rechallenge.

[0006] In a first aspect, the present invention provides a method for evaluating the prognosis or treatment efficacy of non-small cell lung cancer patients who have undergone re-treatment or re-challenge with ICIs, the method comprising:

[0007] (1) Obtain the patient’s SII-PNI score before undergoing ICIs retreat or re-challenge;

[0008] (2) Based on the SII-PNI score, determine the prognostic risk or treatment efficacy of patients undergoing ICI retreat or re-challenge.

[0009] In some implementations, the SII-PNI score is obtained through the patient's pre-SII and pre-PNI scores:

[0010] If pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 2;

[0011] If a patient meets only one of the following criteria: pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 1;

[0012] If pre-SII < 1149.80 and pre-PNI ≥ 47, then the patient's SII-PNI score is 0.

[0013] In some implementations, the pre-SII and pre-PNI are obtained by the following formula:

[0014] pre-SII = P x N / L,

[0015] pre-PNI = Alb + 5x L,

[0016] Where P represents platelet count in units of 10^9 / L, N represents neutrophil count in units of 10^9 / L, L represents lymphocyte count in units of 10^9 / L, and Alb represents albumin concentration in units of g / L.

[0017] In some embodiments, step (2) includes: if the SII-PNI score is 0, the patient has a good prognosis or treatment efficacy; and / or, if the SII-PNI score is 1 or 2, the patient has a poor prognosis or treatment efficacy.

[0018] In some embodiments, step (2) includes comparing the patient with a reference patient who received the same treatment, wherein the reference patient's SII-PNI score and its prognosis or treatment efficacy are known: if the patient's SII-PNI score is less than the reference patient's SII-PNI score, then the patient's prognosis or treatment efficacy is better than the reference patient; if the patient's SII-PNI score is greater than the reference patient's SII-PNI score, then the patient's prognosis or treatment efficacy is worse than the reference patient.

[0019] In some implementations, the prognostic and / or therapeutic efficacy refers to the patient's PFS and / or OS after undergoing retreatment or re-challenge with ICIs.

[0020] In some implementations, the patient is a patient with advanced non-small cell lung cancer.

[0021] In some embodiments, the method further includes displaying the prediction results on a screen or printer, or sending the prediction results to a designated email address, computer, or network storage server via an information sending device.

[0022] In a second aspect, the present invention provides a system for evaluating the prognosis or treatment efficacy of non-small cell lung cancer patients who have undergone re-treatment or re-challenge with ICIs, the system comprising:

[0023] (1) A storage device storing information including: the patient’s SII-PNI score prior to ICI retreat or rechallenge;

[0024] (2) A predictive device that predicts the prognosis and / or treatment efficacy of the patient based on the patient’s SII-PNI score;

[0025] (3) An output device that outputs the predicted results of the prognosis and / or treatment efficacy.

[0026] In some embodiments, the system further includes an input device for inputting:

[0027] a. The SII-PNI score; b. pre-SII and pre-PNI; or c. the patient's platelet count, neutrophil count, lymphocyte count, and albumin prior to ICI retreatment or rechallenge.

[0028] In some embodiments, when the input device is used to input the pre-SII and the pre-PNI, the storage device of the system is also used to store the pre-SII and the pre-PNI. At the same time, the system also includes a computing device for calculating the SII-PNI score based on the pre-SII and the pre-PNI.

[0029] In some embodiments, when the input device is used to input the platelet count, neutrophil count, lymphocyte count, and albumin concentration, the system's storage device is also used to store the platelet count, neutrophil count, lymphocyte count, and albumin concentration; simultaneously, the system also includes a calculation device for calculating the patient's pre-SII and pre-PNI based on the platelet count, neutrophil count, lymphocyte count, and albumin concentration, and for calculating the SII-PNI score based on the pre-SII and pre-PNI.

[0030] In some implementations, the pre-SII and pre-PNI are calculated in the following manner:

[0031] pre-SII = P x N / L,

[0032] pre-PNI = Alb + 5x L,

[0033] Where P represents platelet count in units of 10^9 / L, N represents neutrophil count in units of 10^9 / L, L represents lymphocyte count in units of 10^9 / L, and Alb represents albumin concentration in units of g / L.

[0034] In some implementations, the SII-PNI score is calculated in the following manner:

[0035] If pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 2;

[0036] If a patient meets only one of the following criteria: pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 1;

[0037] If pre-SII < 1149.80 and pre-PNI ≥ 47, then the patient's SII-PNI score is 0.

[0038] In some implementations, the prediction device performs a procedure including the following steps:

[0039] If the SII-PNI score is 0, the patient has a good prognosis or good treatment efficacy; and / or, if the SII-PNI score is 1 or 2, the patient has a poor prognosis or poor treatment efficacy.

[0040] In some implementations, the prediction device performs a procedure including the following steps:

[0041] The patients were compared with reference patients who received the same treatment, wherein the SII-PNI scores, prognoses, or treatment efficacy of the reference patients were known:

[0042] If the patient's SII-PNI score is less than the reference patient's SII-PNI score, then the patient's prognosis or treatment efficacy is better than that of the reference patient.

[0043] If the patient's SII-PNI score is greater than that of the reference patient, then the patient's prognosis or treatment efficacy is worse than that of the reference patient.

[0044] In some implementations, the prognostic and / or therapeutic efficacy refers to the patient's PFS and / or OS after undergoing retreatment or rechallenge with ICIs.

[0045] In some implementations, the patient is a patient with advanced non-small cell lung cancer.

[0046] In some implementations, the output device is a display screen, a printer, or an information transmitting device.

[0047] In some implementations, the information sending device sends the prediction result to a designated email address, computer, or network storage server.

[0048] Based on common knowledge in the field, the above-mentioned preferred conditions can be combined arbitrarily to obtain various preferred embodiments of this disclosure.

[0049] The positive and progressive effects of this disclosure are as follows: This invention provides a convenient and effective method and / or treatment efficacy assessment method for ICI retreatment or rechallenge therapy, and a corresponding assessment system, which helps physicians and patients decide whether to choose ICI retreatment or rechallenge. Furthermore, the assessment index involved in this invention is the SII-PNI score, which can be obtained through a complete blood count (CBC) test. The SII-PNI score is a convenient and cost-effective index, helping to reduce assessment costs. Attached Figure Description

[0050] Figure 1A ROC curves of peripheral blood pre-PNI before (baseline) retreatment or rechallenge of ICIs in patients with advanced non-small cell lung cancer;

[0051] Figure 1B ROC curves of peripheral blood pre-SII before (baseline) retreatment or rechallenge of ICIs in patients with advanced non-small cell lung cancer;

[0052] Figure 2A The relationship between SII-PNI score and progression-free survival after ICI retreatment or re-challenge in advanced non-small cell lung cancer;

[0053] Figure 2B The relationship between SII-PNI score and overall survival after ICIs retreatment or re-challenge in advanced non-small cell lung cancer;

[0054] Figure 3A Multivariate analysis was conducted to show the relationship between different factors and progression-free survival in patients with advanced non-small cell lung cancer who underwent ICI retreatment or re-challenge.

[0055] Figure 3B Multivariate analysis was conducted to show the relationship between different factors and overall survival in patients with advanced non-small cell lung cancer who underwent ICI retreatment or re-challenge.

[0056] Figure 4ATo investigate the prognostic relationship between the SII-PNI score of advanced non-small cell lung cancer in the training set and ICI retreatment or re-challenge.

[0057] Figure 4B To validate the relationship between the SII-PNI score of advanced non-small cell lung cancer and the prognostic outcome of ICI retreatment or re-challenge. Detailed Implementation

[0058] To better understand the present invention, specific embodiments will be given to further illustrate the invention. However, it should be understood that the described embodiments are exemplary embodiments, and the invention can be implemented in various forms and should not be limited to the embodiments set forth herein. Rather, these embodiments are provided so that this invention will be thorough and complete, and will fully convey the scope of the invention to those skilled in the art.

[0059] Example 1

[0060] Data from 311 patients with advanced non-small cell lung cancer who received ICIs were collected and analyzed to explore their relationship with prognosis. Of these, 113 patients underwent ICI rechallenge or retreatment, 90 of whom received immunotherapy retreatment, 23 underwent immunotherapy rechallenge, and 93 underwent routine peripheral blood analysis before and after treatment. The first administration of ICIs was defined as ICI1, and the second cycle of immunotherapy upon re-administration was defined as ICI2. Progression-free survival (PFS1) during the first cycle was defined as the duration from the first administration of ICIs to disease progression or death. Correspondingly, progression-free survival during rechallenge or retreatment was referred to as PFS2. Overall survival (OS1) during the initial treatment phase was the duration from the start of ICI1 to death from any cause or the date of the last follow-up, while OS2 was calculated from the date of retreatment or rechallenge initiation. In the context of ICI2, "retreatment" is defined as a clinical strategy of restarting ICI without intervening in cancer treatment, while "rechallenge" refers to restarting ICI after performing other treatments between two cycles of ICI treatment.

[0061] 1. Relationship between SII-PNI score and ICI retreatment or rechallenge

[0062] Before ICI retreatment or rechallenge, patients undergo peripheral blood routine tests. Based on the results of platelet count (P, unit: 10^9 / L), neutrophil count (N, unit: 10^9 / L), lymphocyte count (L, unit: 10^9 / L), and albumin concentration (Alb, unit: g / L), the systemic immune inflammation index (pre-SII) and prognostic nutritional index (pre-PNI) of patients before immune retreatment / rechallenge are calculated, where pre-SII = P x N / L and pre-PNI = Alb + 5 x L.

[0063] ROC (Receiver Operating Characteristic Curve) analysis was used to analyze the systemic immune inflammatory index (pre-SII) and prognostic nutritional index (pre-PNI) of patients before immune retreat / rechallenge. Results are as follows: Figure 1A-1B As shown in Table 1, the optimal cut-off value for pre-SII was determined to be 1149.80 (AUC = 0.59, sensitivity = 0.32, specificity = 0.93), and the optimal cut-off value for pre-PNI was 47 (AUC = 0.53, sensitivity = 0.54, specificity = 0.67). Based on the cut-off values, patients were divided into three groups, and an SII-PNI score was established:

[0064] (1) Patients with high pre-SII (≥1149.80) and low pre-PNI (<47) scored 2;

[0065] (2) Patients who meet only one of the criteria of high pre-SII (≥1149.80) and low pre-PNI (<47) are given a score of 1;

[0066] (3) Patients with low pre-SII (<1149.80) and high pre-PNI (≥47) score 0.

[0067] Analysis of the relationship between SII-PNI score and prognosis of patients undergoing immunotherapy / re-challenge showed that patients with higher SII-PNI scores had a greater risk and worse prognosis when undergoing immunotherapy / re-challenge. Figure 2A-2B The SII-PNI score can serve as an independent prognostic indicator for lung cancer patients. Figures 3A-3B ).

[0068] Table 1 Summary of ROC curve parameters

[0069] variable Cut-off value Sensitivity Specificity AUC pre-PNI 47 0.54 0.67 0.53 pre-SII 1149.80 0.32 0.93 0.59

[0070] Example 2

[0071] Based on the analysis results of Example 1, a method for evaluating the prognosis or treatment efficacy of non-small cell lung cancer patients who have undergone ICI retreatment or re-challenge is established:

[0072] (1) Obtain the SII-PNI score of the patient before undergoing ICIs retreat or re-challenge.

[0073] (2) Based on the SII-PNI score, determine the prognostic risk or treatment efficacy of patients receiving ICIs retreatment or rechallenge treatment.

[0074] The SII-PNI can be obtained by: obtaining the SII-PNI score based on the patient's pre-SII and pre-PNI:

[0075] If pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 2;

[0076] If a patient meets only one of the following criteria: pre-SII ≥ 1149.80 or pre-PNI < 47, then the patient's SII-PNI score is 1;

[0077] If pre-SII < 1149.80 and pre-PNI ≥ 47, then the patient's SII-PNI score is 0.

[0078] The pre-SII and pre-PNI can be obtained using the following formula:

[0079] pre-SII = P x N / L,

[0080] pre-PNI = Alb + 5x L,

[0081] Where P represents platelet count in units of 10^9 / L, N represents neutrophil count in units of 10^9 / L, L represents lymphocyte count in units of 10^9 / L, and Alb represents albumin concentration in units of g / L.

[0082] In some specific embodiments, step (2) includes: if the SII-PNI score is 0, the patient has a good prognosis or treatment efficacy; and / or, if the SII-PNI score is 1 or 2, the patient has a poor prognosis or treatment efficacy.

[0083] In some specific embodiments, step (2) includes comparing the patient with a reference patient who received the same treatment, wherein the reference patient’s SII-PNI score and its prognosis or treatment efficacy are known: if the patient’s SII-PNI score is less than the reference patient’s SII-PNI score, then the patient’s prognosis or treatment efficacy is better than the reference patient’s; if the patient’s SII-PNI score is greater than the reference patient’s SII-PNI score, then the patient’s prognosis or treatment efficacy is worse than the reference patient’s.

[0084] In some specific ways, the prognostic and / or therapeutic efficacy refers to the patient's PFS and / or OS after undergoing retreatment or re-challenge with ICIs.

[0085] In some specific cases, the patient is a patient with advanced non-small cell lung cancer.

[0086] Example 3

[0087] According to Examples 1-2, a system for evaluating the prognosis or treatment efficacy of non-small cell lung cancer patients who have undergone ICI retreatment or re-challenge is established, the system comprising:

[0088] (1) A storage device for storing the patient’s SII-PNI score prior to ICI retreat or rechallenge;

[0089] (2) A predictive device that predicts the prognosis and / or treatment efficacy of the patient based on the patient’s SII-PNI score;

[0090] (3) An output device that outputs the predicted results of the prognosis and / or treatment efficacy.

[0091] The system may further include an input device for inputting:

[0092] a. The SII-PNI score; b. pre-SII and pre-PNI; or c. the patient's platelet count, neutrophil count, lymphocyte count, and albumin prior to retreatment or rechallenge with ICIs.

[0093] When the input device is used to input pre-SII and pre-PNI, or platelet count, neutrophil count, lymphocyte count, and albumin, the system further includes a computing device, which is used for:

[0094] a. Calculate the SII-PNI score based on pre-SII and pre-PNI:

[0095] If pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 2;

[0096] If a patient meets only one of the following criteria: pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 1;

[0097] If pre-SII < 1149.80 and pre-PNI ≥ 47, then the patient's SII-PNI score is 0;

[0098] And / or,

[0099] b. Calculate the pre-SII and pre-PNI based on the platelet count, neutrophil count, lymphocyte count, and albumin:

[0100] pre-SII = P x N / L,

[0101] pre-PNI = Alb + 5x L,

[0102] Where P represents platelet count in units of 10^9 / L, N represents neutrophil count in units of 10^9 / L, L represents lymphocyte count in units of 10^9 / L, and Alb represents albumin concentration in units of g / L.

[0103] In some cases, the prediction device performs a procedure including the following steps:

[0104] If the SII-PNI score is 0, the patient has a good prognosis or good treatment efficacy; and / or,

[0105] If the SII-PNI score is 1 or 2, the patient's prognosis or treatment efficacy is poor.

[0106] In some cases, the prediction device performs a procedure including the following steps:

[0107] The patients were compared with reference patients who received the same treatment, whose SII-PNI scores, prognoses, or treatment efficacy were known:

[0108] If the patient's SII-PNI score is less than that of the reference patient, then the patient's prognosis or treatment efficacy is better than that of the reference patient; if the patient's SII-PNI score is greater than that of the reference patient, then the patient's prognosis or treatment efficacy is worse than that of the reference patient.

[0109] In some specific ways, the prognostic and / or therapeutic efficacy refers to the patient's PFS and / or OS after undergoing retreatment or re-challenge with ICIs.

[0110] In some specific cases, the patient is a patient with advanced non-small cell lung cancer.

[0111] In some specific embodiments, the output device is a display screen, a printer, or an information sending device that sends the prediction result to a designated email address, computer, or network storage server.

[0112] Example 4

[0113] All patients were randomly assigned 1:1 to a training set (N=47) and a test set (N=46) to validate the system described in Example 3. Results showed that in the training set, patients with a SII-PNI score of 0 had better prognosis and treatment efficacy (longer OS) compared to patients with a SII-PNI score of 1 or 2 (see details). Figure 4A Similarly, in the validation set, patients with a SII-PNI score of 0 also showed better prognosis and treatment efficacy (see details). Figure 4B ).

Claims

1. A system for evaluating the prognosis or treatment efficacy in patients with non-small cell lung cancer who have undergone re-treatment or re-challenge with ICIs, characterized in that, The system includes: (1) A storage device for storing the patient’s SII-PNI score prior to ICI retreat or rechallenge; (2) A predictive device that predicts the prognosis and / or treatment efficacy of the patient based on the patient’s SII-PNI score; (3) An output device that outputs the predicted results of the prognosis and / or treatment efficacy.

2. The system according to claim 1, characterized in that, The system also includes an input device for inputting: a. the SII-PNI score; b. pre-SII and pre-PNI; or c. the patient's platelet count, neutrophil count, lymphocyte count, and albumin concentration prior to ICI retreatment or rechallenge.

3. The system according to claim 2, characterized in that, When the input device is used to input the pre-SII and the pre-PNI, the system's storage device is also used to store the pre-SII and pre-PNI. Simultaneously, the system further includes a computing device used to calculate the SII-PNI score based on the pre-SII and pre-PNI, wherein: If pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 2; If a patient meets only one of the following criteria: pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 1; If pre-SII < 1149.80 and pre-PNI ≥ 47, then the patient's SII-PNI score is 0.

4. The system according to claim 2, characterized in that, When the input device is used to input the platelet count, neutrophil count, lymphocyte count, and albumin concentration, the system's storage device is also used to store the platelet count, neutrophil count, lymphocyte count, and albumin concentration; simultaneously, the system also includes a calculation device, which is used to calculate the patient's pre-SII and pre-PNI based on the platelet count, neutrophil count, lymphocyte count, and albumin concentration, and to calculate the SII-PNI score based on the pre-SII and pre-PNI. pre-SII = P x N / L, pre-PNI = Alb + 5x L, Where P represents platelet count in units of 10^9 / L, N represents neutrophil count in units of 10^9 / L, L represents lymphocyte count in units of 10^9 / L, and Alb represents albumin concentration in units of g / L; The calculation of the SII-PNI score includes: If pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 2; If a patient meets only one of the following criteria: pre-SII ≥ 1149.80 and pre-PNI < 47, then the patient's SII-PNI score is 1; If pre-SII < 1149.80 and pre-PNI ≥ 47, then the patient's SII-PNI score is 0.

5. The system according to any one of claims 1-4, characterized in that, The prediction device performs a procedure including the following steps: If the SII-PNI score is 0, the patient has a good prognosis or good treatment efficacy; and / or, if the SII-PNI score is 1 or 2, the patient has a poor prognosis or poor treatment efficacy.

6. The system according to any one of claims 1-4, characterized in that, The prediction device performs a procedure including the following steps: The patients were compared with reference patients who received the same treatment, wherein the SII-PNI scores and their prognoses or treatment efficacy of the reference patients were known: If the patient's SII-PNI score is less than the reference patient's SII-PNI score, then the patient's prognosis or treatment efficacy is better than that of the reference patient. If the patient's SII-PNI score is greater than that of the reference patient, then the patient's prognosis or treatment efficacy is worse than that of the reference patient.

7. The system according to any one of claims 1-4, characterized in that, The prognostic and / or therapeutic efficacy refers to the patient's PFS and / or OS after undergoing retreatment or re-challenge with ICIs.

8. The system according to any one of claims 1-4, characterized in that, The patient was diagnosed with advanced non-small cell lung cancer.

9. The system according to any one of claims 1-4, characterized in that, The output device is a display screen, a printer, or an information sending device.

10. The system according to claim 9, characterized in that, The information sending device sends the prediction results to a designated email address, computer, or network storage server.

Images