RU2766664C1 - Method for assessing the functional state of elderly and older age patients with malignant nominations for the choice of treatment tactics - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to medicine and can be used to assess the functional state of patients with malignant neoplasms (MN) of elderly and senile age for the choice of treatment tactics. The functional status of the patient is assessed according to the Eastern Cooperative Oncology Group (ECOG) scale. Indicators of the functional and geriatric status of the patient, cognitive functions, gait disturbances, age-associated diseases, nutritional status, age are determined. Indicators are evaluated in points. According to the results of the assessment - 0-10 points - the patient does not need a reduction in drug doses, 11-30 points - a reduction in drug doses by 25% is required, 31-53 points - the patient needs palliative care.

EFFECT: method allows choosing the tactics of treating elderly patients with MN, predicting the risk of complications against the background of systemic chemotherapy, and making a decision on reducing the doses of anticancer drugs by assessing the complex of the most significant indicators.

1 cl, 5 tbl, 3 ex

Description

The invention relates to medicine, namely to oncological diseases, and can be used to assess the functional state of elderly and senile patients with malignant neoplasms to select treatment tactics.

According to the WHO classification, the age of 60–74 years is considered to be elderly, and 75–90 years of age is considered to be senile [1]. The maximum level of cancer incidence in the world is observed in the age group over 60 years.

In the process of aging, the ability of all systems to maintain homeostasis decreases, and the body thus becomes more vulnerable to stress factors, which contributes to the development of cancrophilia, a condition in which the likelihood of malignant transformation of cells increases [4]. However, elderly patients differ in their physical, mental and social status. In turn, geriatric syndromes affect the tolerability of anticancer treatment. In elderly patients with identified geriatric syndromes, 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 anticancer therapy and the quality of life of elderly cancer patients [7, 8].

In turn, geriatric syndromes affect the tolerability of anticancer treatment. In elderly patients with identified geriatric syndromes, 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 anticancer therapy and the quality of life of elderly cancer patients [7, 8].

There is a classical oncological method for assessing the functional state of a patient (Table 1), such as the Eastern Cooperative Oncology Group (ECOG) or the Karnofsky index [11].

The disadvantage of this method: do not reflect functional disorders in cancer patients of the older age group.

Various methods of complex geriatric assessment (CGE) are known - this is a multidisciplinary assessment of the functional status of an elderly person, his physical performance, comorbidity, polypharmacy, cognitive and emotional functions, nutritional status and the need for social support [12, 13]. CGO allows [14]: to diagnose disorders not detected during routine physical examination and history taking; predict severe toxicity associated with treatment; evaluate the overall survival of cancer patients, taking into account various methods of treatment; choose the optimal intensity of treatment. This evaluation may reveal previously unknown geriatric problems and lead to a change in treatment strategy in 20-49% of patients [15].

The disadvantage of the known CGO is that they are not combined into a single system and are not adapted for cancer patients.

The technical result of the invention is the possibility of choosing the tactics of treating elderly and senile patients with cancer, using a new adapted geriatric assessment (developed by the "Adapted Geriatric Questionnaire"), taking into account both the functional and geriatric status of such patients, predicting the risk of complications against the background of systemic chemotherapy and making a decision to reduce the doses of anticancer drugs, taking into account the geriatric and functional status of the patient.

The specified technical result is achieved in a method for assessing the functional state of patients with malignant neoplasms of elderly and senile age for the choice of treatment tactics, including a scoring of the functional state according to the Eastern Cooperative Oncology Group (ECOG) scale, in which the following indicators of the functional and geriatric state of the patient are additionally determined in the scoring : the patient's ability to self-care, including: using public transport easily - 0 points, with partial assistance - 1 point, no - 2 points, moving around the apartment easily - 0 points, with partial assistance - 1 point, no - 2 points, getting out of bed - easy - 0 points, with partial help - 2 points, no - 3 points, dressing / undressing - easy - 0 points, with partial help - 2 points, no - 3 points, eating - easy - 0 points, with partial help - 2 points, no - 3 points, taking a bath, shower - easy - 0 points, with partial help - 2 points, no - 3 points la; cognitive functions, including: orientation in space and time - yes - 0 points, partially - 2 points, no - 3 points, clock drawing test - passed (10 points on the clock drawing test) - 0 points, partially completed (6 -9 points on the clock drawing test) - 2 points, not completed (0-5 points on the clock drawing test) - 3 points; fragility, including: gait disturbance - no - 0 points, lameness - 1 point, with a cane - 2 points, "get up and go" test - completed - 0 points, performed with help - 1 point, not completed - 2 points; age-associated diseases, including: disability - no - 0 points, yes - 1 point; hearing impairment - no - 0 points, moderate - 1 point, strong - 2 points; visual impairment - no - 0 points, moderate - 1 point, strong - 2 points; urination disorders - no - 0 points, yes - 1 point, urination disorders - 2 points; the presence of fractures in history after 60 years - no - 0 points, one - 1 point, more than one - 2 points; the presence of AMI in history - no - 0 points, one - 1 point, more than one - 2 points; the presence of strokes in history - no - 0 points, without paresis - 2 points, the presence of paralysis - 3 points; diabetes - no - 0 points, compensated - 1 point, decompensated - 2 points; anemia - no - 0 points, 1 degree - 1 point, 2 degree - 2 points; nutritional status, including: body mass index (BMI) 19-25 - 0 points, BMI>25 - 1 point, BMI<19 - 2 points; weight loss in the last 3 months - no - 0 points, 1-3 kg - 1 point, >33 kg - 2 points; age - up to 70 years old - 0 points, over 70 years old - 1 point and according to the results of the assessment - 0-10 points - the patient does not need to reduce the doses of drugs, 11-30 points - the doses of drugs need to be reduced by 25%, 31-53 points The patient is in need of palliative care.

All indicators of the functional and geriatric status of the patient are the criteria developed, in the framework of our study, "Adapted geriatric questionnaire in the diagnosis and treatment of cancer patients of elderly and senile age" (Table 2).

<*>Clock drawing test

The patient is given a blank sheet of unlined paper and a pencil. The medical worker says: "Please draw a round clock with numbers on the dial and so that the hands of the clock show fifteen minutes to two." The patient himself must draw a circle, put all 12 numbers in the correct places and draw arrows indicating the correct positions.

The test is completed: a circle is drawn, the numbers are in the correct places, the arrows show the specified time, minor inaccuracies in the location of the arrows.

Test partially passed: more noticeable errors in the placement of the hands, the hands show a completely wrong time, the hands do not fulfill their function (for example, the right time is circled), the numbers on the dial are incorrectly arranged: they follow the reverse order (counterclockwise) or the distance between numbers are not the same.

The test failed: the integrity of the clock is lost, some of the numbers are missing or located outside the circle, the numbers and the dial are no longer connected to each other, the patient's activity shows that he is trying to follow the instruction, but unsuccessfully, or does not attempt to follow the instruction. Interpretation of test results:

10 points - the norm, a circle is drawn, the numbers are in the right places, the arrows show the specified time,

9 points - minor inaccuracies in the location of the arrows,

8 points - more noticeable errors in the location of the arrows,

7 points - the hands show a completely wrong time,

6 points - the arrows do not perform their function (for example, the right time is circled),

5 points - incorrect arrangement of numbers on the dial, they follow in reverse order or the distance between the numbers is not the same,

4 points - the integrity of the clock is lost, some of the numbers are missing or located outside the circle,

3 points - the numbers and the dial are not related to each other,

2 points - the patient tries to perform the test, but without success,

1 point - the patient does not attempt to perform the test.

<**>Get up and go test

The patient is asked to get up from a chair in 15-20 seconds, walk a distance of 3 meters, turn around, come back and sit down again.

The claimed method is based on the results of a study that included 177 patients with metastatic colorectal cancer (mCRC) T1-4N1-2M1 (stage IV) who received line I systemic therapy based on the FOLFOX-6 regimen from 2015 to 2021. The prospective group for assessing and correcting geriatric syndromes included 59 patients with mCRC, and the historical control group (without assessment and correction of geriatric status) in a 1:2 ratio included 118 similarly treated patients with mCRC. To assess the geriatric status and address the issue of the need to reduce drug doses by 25%, the Adapted Geriatric Questionnaire was used.

When assessing the gerontological profile, geriatric syndromes were absent in 10 (24.4%) patients in the elderly group, in 6 (33.3%) patients of middle age; 1 geriatric syndrome was detected in 9 (21.9%) patients older than 60 years and in 6 (33.3%) aged 45-59 years; 2 syndromes each were in 4 (9.7%) and 3 (16.7%) patients for the elderly and middle age, respectively; ≥3 geriatric syndromes were detected in 17 (41.4%) patients, in the group under 60 years in 3 (16.6%) patients. As can be seen from the results obtained, chronological age in itself is not an indicator of old age, both elderly and middle-aged patients can have geriatric syndromes, but in the group of patients over 60 years of age, the number of geriatric syndromes occurring is higher, which should be taken into account when choosing treatment tactics.

Taking into account geriatric status, a dose reduction of 25% before starting systemic treatment was recommended in 16 (27.1%) of 59 patients. In the analysis of the group without assessment of geriatric status - 19 (16.1%) of 118 patients, the reduction of drug doses by 25% was performed during treatment due to severe toxicity.

The clinical efficacy of assessing and correcting geriatric syndromes in patients with mCRC was assessed by the incidence of hematological and non-hematological complications in the group with CHO (n=59) compared with the group without CHO (n=118). Hematological toxicity against the background of first-line systemic therapy based on the FOLFOX-6 regimen was less pronounced in patients with CHO, compared with the group without CHO, and had a statistically significant effect on the degree and frequency of neutropenia (p<0.01). In patients over 60 years of age and middle age against the background of CHO, neutropenia was absent in 80.5% and 50% of patients, respectively, without CHO 35.7% and 66.7%. Grade 3 neutropenia was absent in the group with CGO at both ages, without CGO it was 10.7% and 14.8%) for the elderly and middle age, respectively. Neuropathy of the 1st degree was less common in patients older than 60 years on the background of CHO 12.2%, in patients without CHO 14.2%; neuropathy of the 2nd degree against the background of CHO was not observed (p<0.05). Hepatotoxicity was higher in elderly patients without CHO: grade 1 - 35.7%, grade 2 - 7.1%, grade 3 - 4%; against the background of CHO in patients older than 60 years, only 1 degree hepatotoxicity was detected - 2.4% (p<0.05).

Evaluation and correction of geriatric status has a statistically significant effect on the objective response in patients older than 60 years on the background of first-line systemic therapy based on the FOLFOX-6 regimen (p<0.01). In the 60+ group with CGO: stabilization - 35.3%, partial regression - 50%, progression - 14.7%; in the 60+ group without CGO: stabilization - 53.3%), partial regression - 20%, progression - 20%. Regardless of age, in patients with mCRC on the background of first-line systemic therapy based on the FOLFOX-6 regimen, assessment and correction of geriatric status significantly improves the objective response (p<0.01) and clinically significant response (p<0.05).

Also, the assessment and correction of geriatric syndromes in patients with mCRC receiving the first line of systemic therapy based on the FOLFOX-6 regimen made it possible to perform significantly more resection of isolated liver metastases (20.4%) compared to the group without CHO (3.3%) р <0.05.

As part of the dissertation research, an assessment and analysis of the EFS of patients with mCRC on the background of the first line of therapy in combination with the assessment and correction of geriatric syndromes was carried out. The event was considered to be the progression of the disease, or the occurrence of complications such as PE and acute intestinal obstruction, or intolerable toxicity, requiring a change in line or discontinuation of therapy. Evaluation and correction of geriatric syndromes significantly improves the event-free survival of patients with mCRC. In patients older than 60 years (p=0.02): the median ESF of elderly patients in the group with CHO was 12.0 (9.31-16.96), and in the group without CHO 5.0 (4.68-11 ,one).

The sensitivity score of the adapted geriatric questionnaire was calculated using the formula:

where: PI is the number of true-positive predictions (the number of patients in whom, according to the value of this test, dose reduction was performed); LO - the number of false negative predictions (according to the value of this indicator, it is predicted that the patient does not have enough test scores to perform dose reduction, but in fact it was performed).

Those. 81% of patients who, according to the test results, showed a reduction, really needed a reduction in drug doses.

The specificity score of the adapted geriatric questionnaire was calculated using the formula:

where: IR - the number of true negative predictions (the patient does not need dose reduction);

LP - the number of false positive predictions (according to the value of this test, the need for dose reduction is predicted, but in fact, dose reduction was not required).

Those. 98% of those patients who, according to the test results, did not show reduction, really did not need to reduce the doses of drugs.

The diagnostic performance of the test is expressed as the percentage of true (both positive and negative) test results to the total number of results obtained:

Those. in 93% of cases, according to the test results, a reduction in the doses of drugs is really shown.

The method is confirmed by clinical examples.

Example 1. 0-10 points - the patient does not need to reduce the doses of drugs.

Patient K., 68 years old. Diagnosis: Cancer of the upper ampulla of the rectum cT3NxM1 (hep)/IV st. (GI No. 4751 of 2018: highly differentiated adenocarcinoma of the upper ampulla of the rectum, KRAS+, NRAS-, BRAF-, MSI).

Prior to the start of treatment, testing was performed using the "Adapted Geriatric Questionnaire" according to the claimed method (Table 3).

Treatment: From 02/05/2019 for 6 months - 1st line PCT according to the FOLFOX-6 scheme (oxaliplatin, leucovorin, 5-fluorouracil) No. 13.

Result: complete regression of liver metastases, partial regression of the formation of the upper ampulla of the rectum. Surgical treatment of the primary tumor was performed. Complications of treatment: anemia 1 tbsp.

Example 2. 11-30 points - it is necessary to reduce the doses of drugs by 25%.

Patient G., 80 years old. Diagnosis: PMSZNO: 1. Non-Hodgkin's lymphoma, diffuse large B-cell, CD20+, non-GCB, with co-expression of c-myc and bcl-2. Solitary neoplasm of the right popliteal fossa. 02/06/2017 resection of the neoplasm of the right popliteal fossa. 03/02/2017 necrectomy, sanitation of the purulent focus, repeated biopsy of the neoplasm of the right popliteal fossa. Stabilization against the background of 2 injections of Cyclophosphamide and 4 injections of rituximab. 2. Cancer of the rectum T4N2bM1/IV st. (G1 adenocarcinoma, DPD-medium, TP-low, TS-low, KRAS, NRAS, BRAF were not detected). Multiple mts in the liver, pararectal l / y. 07/13/2017 - unloading colostomy.

Prior to the start of treatment for rectal cancer, testing was performed using the "Adapted Geriatric Questionnaire" according to the claimed method (Table 4).

Treatment: From 09/04/2017 against the background of the 1st line of PCT according to the FOLFOX scheme No. 12. Partial regression. From 05/09/18 to 01/2019 MXT Capecitabine 1000 mg. Progression from 01.2019. From 05.02.2019 to 08.2019, 2nd line of PCT according to the FOLFIRI scheme No. 12. Progression from 11.2019.

Status during therapy with regorafenib from 11.2019 to the present: Stabilization. Complications of treatment: anemia 1 tbsp.

Example 3. 31-53 points - the patient needs palliative care.

Patient 3. 78 years old. Diagnosis: Cancer of the transverse colon cT3NxM1(hep)/IV stage (GI: highly differentiated adenocarcinoma).

At the reception, testing was performed using the "Adapted Geriatric Questionnaire" according to the claimed method (Table 5).

At the reception, accompanied by her husband, all questions about the state of health were answered by the husband. Moves with the support of her husband due to unsteady gait and disorientation, poor vision, dizziness. There is confusion, lack of orientation in time.

Given the patient's condition, severe malnutrition, comorbidities, systemic chemotherapy is associated with a high risk of complications. Symptomatic therapy is recommended: analgesic therapy, nutritional support, consultation with a neurologist, MRI of the brain in order to exclude stroke, brain metastasis.

Based on the results of the study, it can be concluded that in order to increase the effectiveness of the treatment of elderly and senile cancer patients in the clinical practice of oncologists, it is advisable to conduct a comprehensive geriatric examination, an alternative to which an adapted geriatric questionnaire can serve as an alternative in routine clinical practice.

The inventive method allows you to choose the tactics of treating elderly patients with cancer using an adapted geriatric assessment ("Adapted Geriatric Questionnaire"), taking into account both the functional and geriatric status of a cancer patient, predicting the risk of complications during systemic chemotherapy and making a decision on dose reduction anticancer drugs, taking into account the geriatric and functional state of the patient.

Sources of information

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Claims (1)

A method for assessing the functional state of patients with malignant neoplasms of elderly and senile age for choosing treatment tactics, including a scoring of the functional state according to the Eastern Cooperative Oncology Group (ECOG) scale, characterized in that the following indicators of the functional and geriatric state of the patient are additionally determined in the scoring: to self-service, including: using public transport is easy - 0 points, with partial assistance - 1 point, no - 2 points, moving around the apartment is easy - 0 points, with partial assistance - 1 point, no - 2 points, getting out of bed - easy - 0 points, with partial help - 2 points, no - 3 points, dressing / undressing - easy - 0 points, with partial help - 2 points, no - 3 points, eating - easy - 0 points, with partial help - 2 points, no - 3 points, taking a bath, shower - easy - 0 points, with partial help - 2 points, no -3 points; cognitive functions, including: orientation in space and time - yes - 0 points, partially - 2 points, no - 3 points, clock drawing test - passed (10 points on the clock drawing test) - 0 points, partially completed (6 -9 points on the clock drawing test) - 2 points, not completed (0-5 points on the clock drawing test) - 3 points; fragility, including: gait disturbance - no - 0 points, lameness - 1 point, with a cane - 2 points, "get up and go" test - completed - 0 points, performed with help - 1 point, not completed - 2 points; age-associated diseases, including; disability - no - 0 points, yes - 1 point; hearing impairment - no - 0 points, moderate - 1 point, strong - 2 points; visual impairment - no - 0 points, moderate - 1 point, strong - 2 points; urination disorders - no - 0 points, yes - 1 point, urination disorders - 2 points; the presence of fractures in history after 60 years - no - 0 points, one - 1 point, more than one - 2 points; the presence of AMI in history - no - 0 points, one -1 point, more than one - 2 points; the presence of strokes in history - no - 0 points, without paresis - 2 points, the presence of paralysis - 3 points; diabetes - no - 0 points, compensated - 1 point, decompensated - 2 points; anemia - no - 0 points, 1 degree - 1 point, 2 degree - 2 points; nutritional status, including: body mass index (BMI) 19-25 - 0 points, BMI>25 - 1 point, BMI<19 - 2 points; weight loss in the last 3 months - no - 0 points, 1-3 kg - 1 point, >33 kg - 2 points; age - up to 70 years old - 0 points, over 70 years old - 1 point and according to the results of the assessment - 0-10 points - the patient does not need to reduce the doses of drugs, 11-30 points - the doses of drugs need to be reduced by 25%, 31-53 points The patient needs palliative care.