Method for assessing condition of inoperable patients with resectable pancreatic cancer to determine possibility of chemotherapy and radiation therapy

Abstract

FIELD: oncology.SUBSTANCE: used to assess the condition of inoperable patients with resectable pancreatic cancer and determine the possibility of carrying out chemotherapy and radiation therapy. The method includes determining the patient's age, history of acute cerebrovascular accident, acute myocardial infarction, diabetes mellitus, calculating the body mass index and scoring the condition according to the Eastern Cooperative Oncology Group (ECOG) scale. In addition, the patient is assessed for the presence of uncorrected hypertension, the presence of uncorrected cardiac arrhythmias, the presence and stage of chronic heart failure, the duration of the acute myocardial infarction, the presence of an implanted pacemaker, the presence and stage of respiratory failure, the presence of chronic obstructive pulmonary disease and the calculation of the forced expiratory volume in 1 second, the presence and stage of chronic kidney disease, changes in the level of the tumor marker CA 19–9 in the peripheral blood and carcinoembryonic antigen, the presence of liver cirrhosis and determination of the severity class according to the Child-Pugh classification. The obtained data are then assigned points in accordance with Table 1 contained in the description. The points obtained are summed up and if the sum is from 7–15 points, chemo- and radiation therapy is carried out without dose reduction; if the sum is from 16–23, chemo- and radiation therapy is carried out with dose reduction; and if the sum is 24-32, no treatment is carried out.EFFECT: method ensures the selection of inoperable patients with resectable pancreatic cancer for chemotherapy and radiation therapy.1 cl, 1 tbl, 3 ex

Description

[0001] The invention relates to the field of medicine, namely oncology, and can be used to assess the condition of inoperable patients with resectable pancreatic cancer and determine the possibility of antitumor treatment.

[0002] Pancreatic cancer (PC) is characterized by an extremely poor prognosis and low survival rates. The peak incidence of adenocarcinoma occurs at the age of 70-80 years, and the presence of comorbidities in these patients increases the risk of postoperative complications (Kaprin A.D. et al., 2024; Klein A.P., 2021). At the time of diagnosis, most patients are diagnosed with advanced stages of the disease: only 25% of patients have tumors at stages I-II. One-year survival does not exceed 25%, and five-year survival is 10% (Kaprin A.D. et al., 2024; Stoop T.F., et al., 2025).

[0003] Today, there are various methods of treating prostate cancer.

[0004] Surgery is the standard treatment for resectable adenocarcinoma of the head of the pancreas. However, even after radical surgery (R0), the recurrence rate reaches 80% (Fatima, J., et al, 2010; Griffin, JF, et al, 1990). Five-year survival remains low, at only 17%. The median survival after recurrence is extremely short: 7 months for local recurrence of the disease and 3 months for liver metastases (Sperti C., et al, 1997). Surgical intervention in weakened patients with resectable pancreatic cancer, with concomitant pathology and comorbid conditions, is accompanied by a high risk of complications, such as acute heart failure, thromboembolic complications, multiple organ failure, bleeding, fluctuations in glucose levels, pneumonia, anastomotic leakage, prolonged stay in the intensive care unit and a difficult recovery period.

[0005] For inoperable tumors, the most effective treatment methods are regional chemotherapy and radiation therapy (Patent No. RU 2798679 C1; Patent No. RU 2528881 C1; Kozlov A.V., et al., 2019). However, these treatment methods can lead to complications such as post-embolization syndrome, pancreatitis, gastrointestinal bleeding, toxic liver damage, bone marrow suppression, and severe asthenia. Therefore, when conducting antitumor treatment in inoperable patients with resectable pancreatic cancer, it is necessary to carefully select the patient based on concomitant pathology and comorbidity to reduce the risk of complications.

[0006] Considering the peculiarities of the course of prostate cancer, the majority of patients over 70 years of age at the time of application already have contraindications not only to radical surgical intervention, but also to other treatment methods, such as chemotherapy and radiation therapy due to severe somatic status.

[0007] Standard treatment protocols for such inoperable patients with resectable pancreatic cancer include capecitabine monotherapy or palliative care. However, these methods are not sufficiently effective: capecitabine monotherapy produces an objective response in only 10% of patients and disease stabilization in 40%, with a median survival of 6 months. This treatment does not improve quality of life or life expectancy.

[0008] In our professional treatment of inoperable patients with resectable pancreatic cancer, we concluded that the initial somatic status and the management of comorbidities are critical for determining the feasibility of antitumor treatment. This group of patients (inoperable patients with resectable pancreatic cancer) is highly susceptible to life-threatening complications caused by the toxicity of antitumor treatment. Therefore, the need arose to develop a scale for assessing the somatic status of inoperable patients.

[0009] Despite the abundance of performance status scales used in oncology for treatment decision-making, their prognostic value and objectivity remain limited when applied to risk assessment in inoperable patients with resectable pancreatic cancer.

[0010] The ECOG / WHO scale (Kelly CM and Shahrokni A., 2016) or the Karnofsky index are used to determine the level of physical activity and the patient's overall condition. However, these classical methods have a significant drawback: they are unable to fully reflect functional impairment in elderly and senile patients, significantly limiting their diagnostic value in this category of patients.

[0011] The ASA scale (American Society of Anesthesiologists. (2020)), developed by the American Society of Anesthesiologists to assess patients' physical status, is the leading method for determining perioperative risks. It has significant limitations when assessing the condition of elderly patients, due to several factors. Firstly, it is characterized by a one-dimensional assessment, as it focuses exclusively on the patient's physical condition, ignoring age-related characteristics and the complex of comorbidities that are particularly important for the elderly. Furthermore, the system demonstrates subjectivity in assessment: different specialists may classify the condition of the same elderly patient differently, which creates significant difficulties in treatment planning. A significant drawback is the lack of age gradation: the scale does not distinguish between natural age-related changes and pathological conditions.It should also be noted that the ASA score has insufficient prognostic value, as it does not adequately assess the risk of postoperative complications in elderly patients, potentially leading to an underestimation of the patient's actual condition. Finally, the limited range of parameters does not account for risk factors specific to elderly patients, such as sarcopenia, cognitive impairment, and polypharmacy (multiple drug therapy).

[0012] The frailty index has several significant limitations when used to assess elderly cancer patients. Firstly, this method does not fully reflect the severity of the cancer patient's condition, as it does not take into account the specific characteristics of the malignant process and its impact on the patient's body. Secondly, in cancer cases, the index does not adequately predict the tolerability of antitumor treatment, the risk of complications, and the likelihood of an adverse outcome.

[0013] The third important drawback is that the fragility index does not take into account: the severity of the tumor process, the nature of the antitumor therapy and the dynamics of the patient's condition during treatment.

[0014] Furthermore, the technique requires significant time investment to conduct a full examination, which may be problematic for weakened cancer patients.

[0015] In the context of oncological diseases, these limitations significantly reduce the diagnostic value of the frailty index as an independent tool for assessing the patient's condition.

[0016] Comprehensive geriatric assessment of elderly cancer patients faces a number of significant limitations. First of all, conducting a full examination is time-consuming, which can be problematic for frail cancer patients in critical condition.

[0017] A serious limitation is the lack of availability of qualified specialists. Not all medical institutions have sufficient physicians of various specialties to conduct a comprehensive assessment. This is especially important given that such an approach requires the participation of a multidisciplinary team of specialists.

[0018] Assessment results can vary significantly depending on the experience and qualifications of the physicians conducting the examination, creating the problem of subjectivity in the interpretation of the obtained data. Furthermore, it is not always possible to ensure regular monitoring of the patient's condition and timely adjustments to the treatment plan, which reduces the effectiveness of the entire approach.

[0019] Technical limitations also play a significant role: some assessment components require specialized diagnostic equipment that may not be available at some medical institutions. Furthermore, standard geriatric scales do not always take into account the specific features of the cancer disease and the specifics of the antitumor treatment.

[0020] Finally, a comprehensive geriatric assessment does not always accurately predict the patient's condition during anticancer therapy, creating additional challenges in treatment planning. Many important factors affecting a cancer patient's condition may remain outside the scope of a standard assessment, necessitating the development of specialized, tailored approaches specifically for this patient population.

[0021] Thus, none of the existing methods provides an objective and comprehensive assessment of risks in this category of patients, which necessitates the development of a new specialized scale.

[0022] The closest to the proposed method is the method for assessing the functional state of elderly and senile patients with malignant neoplasms to select treatment tactics in Russian patent No. 2766664 C1, which we have chosen as a prototype.

[0023] The prototype evaluates the patient's functional status using the Eastern Cooperative Oncology Group (ECOG) scale. It measures the patient's functional and geriatric status, cognitive function, gait disturbances, age-associated diseases, nutritional status, and age. These indicators are scored. A score of 0-10 indicates no need for drug dose reduction, 11-30 indicates a 25% dose reduction, and 31-53 indicates a need for palliative care. This method enables the selection of treatment strategies for elderly patients with malignant neoplasms, the prediction of the risk of complications during systemic chemotherapy, and the decision to reduce anticancer drug doses by assessing a combination of the most significant indicators.

[0024] According to this method, it can be concluded that in order to improve the effectiveness of treatment of elderly and senile patients with malignant neoplasms in the clinical practice of oncologists, it is advisable to conduct a comprehensive geriatric examination, an alternative to which in routine clinical practice can be an adapted geriatric questionnaire.

[0025] The claimed method allows for the selection of treatment tactics for elderly patients with malignant neoplasms receiving systemic chemotherapy using an adapted geriatric assessment (the “Adapted Geriatric Questionnaire”) that takes into account both the functional and geriatric status of the cancer patient.

[0026] The presented prototype is certainly an improvement over using the ECOG scale alone, as it attempts to account for the multifactorial nature of the elderly cancer patient's condition. However, it suffers from fundamental shortcomings typical of complex geriatric scales: subjectivity, cumbersomeness, and lack of validation for narrow but complex patient groups (such as pancreatic cancer). This limits its practical application and reliability in making critical treatment decisions. A more specialized, objective, and easy-to-use tool is needed for this patient population.

[0027] The technical result of the invention is to provide the possibility of selecting inoperable patients with resectable pancreatic cancer for specific antitumor treatment using a new adapted assessment scale.

[0028] This result is achieved by the fact that in the known method for assessing the condition of inoperable patients with resectable pancreatic cancer to determine the possibility of antitumor treatment, including determining the patient's age, the presence in the anamnesis of acute cerebrovascular accident (ACVA), acute myocardial infarction, diabetes mellitus, calculating the body mass index (BMI) and a point assessment of the condition according to the Eastern Cooperative Oncology Group (ECOG) scale, according to the invention, the following indicators are additionally taken into account in the patient, namely: the presence of uncorrected hypertension, the presence of uncorrected cardiac arrhythmias, the presence and stage of chronic heart failure, the duration of the previous acute myocardial infarction, the presence of an implanted pacemaker, the presence and stage of respiratory failure, the presence of chronic obstructive pulmonary disease and the calculation of the forced expiratory volume in 1 second (FEV1),the presence and stage of chronic kidney disease, changes in the level of the tumor marker CA 19-9 in the peripheral blood and carcinoembryonic antigen (CEA), the presence of liver cirrhosis and determination of the severity class according to the Child-Pugh classification, then the obtained data are assigned points in accordance with Table 1 contained in the description, the obtained points are summed up and with a sum of 7-15 points, antitumor treatment is carried out without dosage reduction, with a sum of 16-23, antitumor treatment is carried out with dosage reduction and with a sum of 24-32, antitumor treatment is not carried out.

[0029] Table 1 - scale for assessing the condition of inoperable patients with resectable pancreatic cancer

[0030] Criteria Points Age up to 60 years more than 60 years 1 point 2 points Diabetes mellitus No compensated decompensated 0 points 1 point 2 points Uncorrected hypertension No Yes 1 point 2 points Uncorrectable cardiac arrhythmias No Yes 1 point 2 points Chronic heart failure No I - IIA stage IIB - III stage 0 points 1 point 2 points Past acute myocardial infarction No more than 6 months ago less than 6 months ago 0 points 1 point 2 points Acute cerebrovascular accident No more than 6 months ago less than 6 months ago 0 points 1 point 2 points Obesity BMI less than 40 BMI over 40 1 point 2 points Implanted pacemaker No Yes 1 point 2 points Respiratory failure No I - II degrees III degree 0 points 1 point 2 points Chronic obstructive pulmonary disease FEV1 greater than 50% FEV1 less than 50% 1 point 2 points WHO / ECOG Patient Severity Assessment Scale 0 1-2 more than 2 0 points 1 point 2 points CA level 19-9 less than 1000 U / ml more than 1000 U / ml 1 point 2 points Carcinoembryonic antigen (CEA) level less than 100 ng / ml more than 100 ng / ml 1 point 2 points Chronic kidney disease No stage C1 - C4 stage C5 0 points 1 point 2 points Child-Pugh liver cirrhosis severity scale No class A-B class C 0 points 1 point 2 points TOTAL (Sum of points)

[0031] The highest incidence rate of cancer in the world is observed in the age group over 60 years (Malignant neoplasms in Russia in 2024 (incidence) / edited by A.D. Kaprin [et al.] - Moscow: P.A. Herzen Moscow Oncology Research Institute - branch of the National Medical Research Center of Radiology of the Ministry of Health of the Russian Federation, 2025. - ill. - 178 p.). In such patients, the toxic profile of systemic and radiation treatment increases, the risk of early postoperative complications increases, which in turn increases the duration of hospitalization, reduces the effectiveness of antitumor therapy and the quality of life of elderly cancer patients.

[0032] Cardiological parameters have not previously been used to select patients for anticancer treatment. Chemotherapeutic drugs can cause fluctuations in blood pressure and hypertensive crises, increasing the risk of acute cerebrovascular accident, kidney damage, and acute heart failure. Heart rhythm disturbances, such as atrial fibrillation, increase the risk of thromboembolic complications. Patients with chronic heart failure (CHF), depending on the stage, have reduced functional reserve. This parameter is important to consider, as chemotherapy drugs can lead to decompensation and the development of life-threatening acute heart failure. The stage of CHF determines the suitability and safety of a specific chemotherapy regimen. Anticancer treatment is contraindicated in patients with acute myocardial infarction (AMI less than 6 months ago) due to the high risk of recurrent infarction and death.The presence of an implanted cardiac pacemaker (ICP) is not a contraindication to antitumor treatment; however, it is important to assess the reason for its installation, ensure its proper functioning, and rule out an infectious process in the implantation area.

[0033] Respiratory system assessment is crucial for patient selection for anticancer treatment. Chemotherapy drugs can cause toxic pneumonitis and pulmonary fibrosis. Patients with respiratory failure (RF) are at risk for complications such as severe, intractable respiratory failure requiring mechanical ventilation. Chronic obstructive pulmonary disease (COPD) limits the patient's functional capacity. Before initiating anticancer treatment, COPD therapy should be adjusted and medications with pulmonary toxicity should be discontinued.

[0034] Renal excretion is a function of the renal pathway responsible for eliminating most cytostatic drugs. Chronic kidney disease (CKD) impairs kidney function, leading to drug accumulation in the blood, thereby increasing toxicity, which manifests as bone marrow suppression, mucositis, and neuropathy. The risk of acute kidney injury during treatment also increases.

[0035] The presence of liver cirrhosis increases the risk of liver failure, bleeding, and severe infections. Liver function testing using the Child-Pugh score, due to its key role in the biotransformation of cytostatic drugs and the production of proteins that regulate coagulation and other physiological processes, allows one to assess the risk of toxic effects after regional chemotherapy, radiation therapy, or systemic chemotherapy.

[0036] Determining the levels of the CA 19-9 and CEA tumor markers is used to assess the extent of the tumor process. High initial values ​​correlate with a larger tumor mass and are an unfavorable prognostic factor. Monitoring marker dynamics—before, during, and after treatment—is an important tool for monitoring the effectiveness of therapy: a decrease in concentration indicates a response to treatment, while an increase indicates disease progression.

[0037] The points obtained are summed up, and a decision on the possibility of treatment is made based on the final score:

[0038] - 7-15 points: antitumor treatment is carried out in standard dosages (without reduction).

[0039] Regional chemotherapy, radiation therapy, and systemic chemotherapy are recommended without reducing the doses of chemotherapy drugs and radiation.

[0040] - 16-23 points: antitumor treatment is carried out with a reduction in drug dosage (taking into account the increased risk of toxicity).

[0041] Regional chemotherapy, radiation therapy and systemic chemotherapy with a reduction in the doses of chemotherapy drugs and radiation are recommended.

[0042] - 24-32 points: Antitumor treatment is not performed due to the high risk of complications. Palliative care is recommended.

[0043] Thus, patients with resectable pancreatic cancer, recognized as inoperable based on somatic status and receiving palliative therapy, after a comprehensive assessment according to the developed scale, can be selected for antitumor treatment.

[0044] The proposed invention is explained by examples.

[0045] Example 1

[0046] Patient G., 83 years old. Diagnosed with adenocarcinoma of the head of the pancreas cT3N0M0, stage IIA, G2, came to our center for consultation. She did not receive specific antitumor therapy. A comprehensive assessment was performed using the scale we developed. Age 83 years - 2 points; Uncorrected hypertension (Stage III hypertension, Stage 2 arterial hypertension) - 2 points; Non-correctable heart disease - 1 point, Chronic heart failure stage IIA - 1 point; BMI 27.2 - 1 point; Chronic obstructive pulmonary disease, FEV 1 87% - 1 point; ECOG scale: 2 points - 2 points; CA 19-9 level: 446 U / ml - 1 point; CEA level: 7.1 ng / ml – 1 point. The total score was 12 points. The patient was offered antitumor treatment without reducing the dosage of chemotherapy and radiation therapy.

[0047] From February 22, 2024, over a period of 3 months, the patient underwent 3 courses of radiochemotherapy using the GemOx regimen. The resulting thrombocytopenia did not require drug correction. The patient then underwent a course of radiation therapy in a multifractionated mode from May 14, 2024, to May 31, 2024 (ROD 2 Gy, SOD 56 Gy). According to follow-up examinations six months after the start of specific antitumor treatment, the patient has stabilized the oncological process. According to MSCT of the abdominal organs from June 20, 2024, the tumor decreased in size from 54x28 to 20x14 mm. According to 18F-FDG PET-CT data from June 25, 2024, the radiopharmaceutical uptake level decreased from SUV=6.3 to 4.7. No distant metastases were detected. The CA 19-9 tumor marker level decreased from 446 to 277 U / mL, and the CEA level decreased from 7.1 to 3.6 ng / mL.The patient is recommended to be under the supervision of an oncologist at the place of residence (MSCT of the abdominal cavity once every 2 months, monitoring of specific markers once every 2 months; PET CT of the whole body with 18F-FDG once every 6 months).

[0048] Example 2

[0049] Patient I., 82 years old. Diagnosed with adenocarcinoma of the head of the pancreas cT2N0M0, stage IB, G1, he came to our center for a consultation. He did not receive specific antitumor therapy. A comprehensive assessment was performed using the scale we developed. Age 82 years - 2 points; Diabetes mellitus type 2, decompensated - 2 points; Uncorrected hypertension (stage III hypertension, stage 3 arterial hypertension) - 2 points; Uncorrectable cardiac arrhythmias such as permanent atrial fibrillation and flutter - 2 points; Chronic heart failure stage IIB - 2 points; Acute cerebrovascular accident more than 6 months ago - 1 point; Obesity stage 2, BMI 36.3 - 1 point; Chronic obstructive pulmonary disease, FEV1 83% - 1 point; ECOG scale: 3 points - 2 points; CA 19-9 level: 107 U / ml - 1 point; CEA level: 9.6 ng / ml - 1 point. A total of 17 points on the scale.The patient was offered antitumor treatment with a reduction in the dosage of chemotherapy drugs and radiation therapy.

[0050] On May 17, 2023, the patient underwent two courses of radiotherapy using the GemOx regimen with a 25% dose reduction, administered every three weeks. Grade 1 gastrointestinal complications (nausea and vomiting) were managed with medication within 6 hours. The patient then underwent a course of radiation therapy using a daily split-dose regimen: a single focal dose of 2 Gy twice daily at 6-hour intervals, divided into 25 fractions for a total focal dose of 50 Gy. Grade 1 hematologic toxicity, manifested by anemia, was observed but did not require medication. Follow-up examinations 6 months after the start of specific antitumor treatment showed stabilization of the patient's oncological process. An abdominal CT scan on August 29, 2023, showed a tumor size reduction from 38x36mm to 27x23mm. A PET / CT scan with 18F-FDG on January 6, 2023, showed tumor stabilization. No distant metastases were detected.The CA 19-9 tumor marker level decreased from 107 to 74 U / ml, and the CEA level from 9.6 to 5.3 ng / ml. The patient was advised to remain under the supervision of a local oncologist (MSCT of the abdominal cavity every 2 months, monitoring of specific markers every 2 months; whole-body PET CT with 18F-FDG every 6 months).

[0051] Example 3

[0052] Patient B, 74 years old. Diagnosed with adenocarcinoma of the head of the pancreas cT3N1M0, stage IIB, G2, came to our center for a consultation. He did not receive specific antitumor therapy. A comprehensive assessment was performed using the scale we developed. Age 74 years - 2 points; Diabetes mellitus type 2, decompensated - 2 points; Uncorrected hypertension (hypertension stage II, arterial hypertension stage 3) - 2 points; No uncorrectable heart rhythm disturbances - 1 point; Chronic heart failure stage III - 2 points; Acute myocardial infarction 3 months ago - 2 points; Obesity stage 3, BMI 41.7 - 2 points; Respiratory failure stage II - 1 point; Chronic obstructive pulmonary disease, FEV1 72% - 1 point; ECOG scale: 3 points - 2 points; CA 19-9 level: 8534 U / ml - 2 points; CEA level: 177.3 ng / ml - 2 points; Chronic kidney disease C3 - 1 point. Total: 24 points on the scale.

[0053] The patient is not recommended to undergo antitumor treatment due to the high risk of complications. Monitoring by a local oncologist and treatment of comorbidities by specialized specialists are recommended.

[0054] The proposed method was successfully used in 91 patients with resectable pancreatic cancer, but inoperable due to severe comorbidities. Thirty-eight patients received regional chemotherapy alone, 29 of whom received standard-dose chemotherapy, and 9 with dose reduction. Thirty-three patients received regional chemotherapy in combination with radiation therapy, 21 of whom received standard-dose chemoradiation, and 12 with dose reduction. Antitumor treatment was not recommended for 20 patients due to the high risk of complications. There were no deaths or adverse events higher than grade 2 according to the NCI CTCAE criteria, v. 5.0. Toxic complications of grades 1-2 were noted in 21 patients who received only regional chemotherapy and in 27 patients who received regional chemotherapy in combination with radiation therapy.

[0055] The proposed method offers a significant advantage over traditional approaches: it allows us to identify patients with resectable pancreatic cancer from a severe group of inoperable patients who are denied polychemotherapy and who can be treated with a modern and effective antitumor treatment approach. Thus, palliative or symptomatic therapy in this group of patients can be supplemented or replaced with active antitumor treatment.

[0056] The proposed method is easily reproduced by a specialist in this field.

[0057] The method was developed in the surgical department No. 2 (abdominal oncology and X-ray surgical methods of diagnosis and treatment) of the Federal State Budgetary Institution "Russian Scientific Center of Radiology and Surgery named after Academician A.M. Granov" of the Ministry of Health of the Russian Federation and passed clinical testing on 91 patients with a positive result.

Claims

A method for assessing the condition of inoperable patients with resectable pancreatic cancer to determine the possibility of chemotherapy and radiation therapy, including determining the patient's age, history of acute cerebrovascular accident, acute myocardial infarction, diabetes mellitus, calculating the body mass index and scoring the condition according to the Eastern Cooperative Oncology Group (ECOG) scale, characterized in that the following indicators are additionally taken into account in the patient, namely: the presence of uncorrected hypertension, the presence of uncorrected cardiac arrhythmias, the presence and stage of chronic heart failure, the duration of the acute myocardial infarction, the presence of an implanted pacemaker, the presence and stage of respiratory failure, the presence of chronic obstructive pulmonary disease and the calculation of the forced expiratory volume in 1 s, the presence and stage of chronic kidney disease,change in the level of the tumor marker CA 19-9 in the peripheral blood and carcinoembryonic antigen, the presence of liver cirrhosis and determination of the severity class according to the Child-Pugh classification, then the obtained data are assigned points in accordance with Table 1 contained in the description, the obtained points are summed up and with a sum of 7-15 points, chemo- and radiation therapy is carried out without dose reduction, with a sum of 16-23, chemo- and radiation therapy is carried out with dose reduction and with a sum of 24-32, treatment is not carried out.