RU2793519C2 - Method of reduction of the expression of chronic pain syndrome in patients with pancreatic cancer with functional status ecog 0-2 points - Google Patents

Abstract

FIELD: medicine.

SUBSTANCE: invention relates to oncology, in particular to methods of palliative care for patients with malignant neoplasms of the abdominal cavity and retroperitoneal space, suffering from chronic abdominal pain syndrome. The invention relates to medicine, namely to oncology, and can be used to reduce the severity of chronic pain in patients with pancreatic cancer. The method involves conducting courses of monochemotherapy with gemcitabine at a dosage of 750–1,000 mg/m² IV on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy. HIFU-therapy sessions are carried out daily, except for the days of administration of the chemotherapy drug on a low-energy device with an ultrasonic flow intensity of 2 kW/cm², the number of pulses per point is 200, the pulse duration is 200 ms, the pause duration is 50 ms, the distance between the points along the axes x/y/z = 3/3/7 mm. If the tumor size is up to 2.0 cm, for one course of HIFU therapy, 4 sessions are performed with an exposure duration of up to 30 minutes, or 3 sessions are performed from 31 to 45 minutes, or 2 sessions are performed from 46 to 60 minutes. If the tumor size is from 2.1 to 4.0 cm, then for one course of HIFU therapy, 5 sessions are performed with an exposure duration of up to 30 minutes, or 4 sessions are performed from 31 to 45 minutes, or 3 sessions are performed from 46 to 60 minutes. If the tumor size is from 4.1 to 6.0 cm, then for one course of HIFU therapy, 6 sessions are performed with an exposure duration of up to 30 minutes, or 5 sessions are performed from 31 to 45 minutes, or 4 sessions are performed from 46 to 60 minutes. If the tumor size is from 6.1 to 8.0 cm, then for one course of HIFU therapy, 7 sessions are performed with an exposure duration of up to 30 minutes, or 6 sessions are performed from 31 to 45 minutes, or 5 sessions are performed from 46 to 60 minutes. If the tumor size is more than 8.0 cm, then for one course of HIFU therapy, 8 sessions are performed with an exposure duration of up to 30 minutes, or 7 sessions are performed from 31 to 45 minutes, or 6 sessions are performed from 46 to 60 minutes.

EFFECT: use of the invention makes it possible to increase the frequency of pain syndrome control after 6 months of combined therapy, by achieving stabilization and/or partial response of the primary focus, a low degree of cytostatic toxicity and the absence of a negative effect of treatment on the functional status of patients.

1 cl, 2 tbl, 15 ex

Description

The invention relates to medicine, namely to oncology, in particular to methods of palliative care for patients with malignant neoplasms of the abdominal cavity and retroperitoneal space, suffering from chronic abdominal pain syndrome.

In the treatment of patients with pancreatic cancer (PCa), a decrease in the severity of tumor-mediated abdominal pain syndrome can be observed while receiving systemic drug therapy. For the purpose of pain relief, various invasive procedures can be performed or radiation therapy can be performed in the form of various techniques.

Today, various endoscopic methods of blockade of the celiac plexus are actively performed under the control of endosonography. The execution technique includes direct puncture of the celiac ganglion followed by injection of a neurolytic agent (ethanol). The injection starts from the deepest part of the ganglion and is performed while the needle is being withdrawn. This procedure reduces the intensity of pain in 74.5-85.2% of patients with prostate cancer in the absence of complications characteristic of percutaneous technique (Puli S.R., Reddy J.B., Bechtold M.L., Antillon M.R., Brugge W.R. EUS-guided celiac plexus neurolysis for pain due to chronic pancreatitis or pancreatic cancerpain: a meta-analysis and systematic review Dig Dis Sci 2009;54(11):2330-7). The main side effects that occur after the intervention are pain at the puncture site (96%), diarrhea (44%), hypotension (38%) (Eisenberg E., Carr D.B., Chalmers T.C. Neurolyticceliac plexus block for treatment of cancer pain: a meta -analysis Anesth Analg 1995;80(2):290-295).

However, this method is used purely for symptomatic purposes and does not affect the course of the underlying tumor disease.

It is known to conduct stereotactic radiation therapy with SOD 33 Gy in 5 fractions in combination with gemcitabine at a dose of 1000 mg/m ² in patients with locally advanced prostate cancer, which makes it possible to statistically significantly reduce the level of pain according to the QLQ-PAN26 questionnaire in patients 4 months after radiotherapy (p = 0.001) (Herman JM, Chang DT, Goodman KA, Dholakia AS, Raman SP, Hacker-Prietz A, Iacobuzio-Donahue CA, Griffith ME, Pawlik TM, Pai JS, O'Reilly E, Fisher GA , Wild AT, Rosati LM, Zheng L, Wolfgang CL, Laheru DA, Columbo LA, Sugar EA, Koong AC. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015 Apr. 1;121(7):1128-37).

However, this method of therapy is characterized by the presence of severe adverse events: early radiation complications of grade 3 and above are represented by a gastrointestinal ulcer (2%), an increase in the level of hepatic blood enzymes (10.2%), dehydration (2%), lympho- (8.2% ), neutro- (2%), thrombocytopenia (2%); late - the development of a fistula (2.1%) and ulcers of the gastrointestinal tract (6.4%), migration of the biliary stent (2.1%), gastrointestinal bleeding (2.1%) (Herman J.M., Chang D.T., Goodman K.A. , et al. Phase 2 multi-institutional trial evaluating gemcitabine and stereotactic body radiotherapy for patients with locally advanced unresectable pancreatic adenocarcinoma. Cancer. 2015;121:1128-1137).

A known method of implantation of radioactive grains of iodine-125 (brachytherapy) in patients with prostate cancer, which allows to achieve control of the level of pain in 79.7-91% of cases of treatment (Han Q., Deng M., Lv Y., et al. Survival of patients with advanced pancreatic cancer after iodine125 seeds implantation brachytherapy: A meta-analysis Medicine (Baltimore) 2017;96(5):e5719 Gai B, Zhang F Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer J Cancer Res Ther. 2018;14(7):1455-1462).

However, this method is invasive and is also characterized by a fairly wide range of side effects. The main complications of brachytherapy for prostate cancer are bloating, nausea, vomiting, loss of appetite, gastroparesis, radiation gastritis, duodenitis, enteritis, pancreatic fistula formation, ascites, fever, grain migration (Tang Y., Yu J.P., Zhang D.W. The incidence of pancreatic fistula after 125I seed implantation in treatment of advanced pancreatic cancer and the influencing factors J Abdom Surg 2016;29:60-63 Huang H.J., Jiang Y., Wu B.Q., et al. Complications and prognosis of intraoperative iodine-125 seed implantation therapy Folkert M.R., Gottumukkala S., Nguyen N.T., et al. Review of brachytherapy complications - Upper gastrointestinal tract.Brachytherapy. 2020;S1538-4721( 20):30254-3).

A known method of high-intensity focused ultrasound therapy (High Intensive Focused Ultrasound, HIFU-therapy) is a non-invasive method of local exposure, the main biological effects of which are thermal and cavitation damage to tumor cells, destruction of small tumor blood vessels, local and systemic immune response to cellular decay products ( Zhou Y. F. HIFU in tumor ablation World J Clin Oncol 2011;2(1): 8-27 Renske J. E. van den Bijgaart, Dylan C. Eikelenboom, Martijn Hoogenboom, Jurgen J. Fütterer, Martijn H. den Brok, Gosse J Thermal and mechanical high-intensity focused ultrasound: perspectives on tumor ablation, immune effects and combination strategies Cancer Immunol Immunother 2017;66(2):247-258.

However, two types of ultrasonic guided devices are mainly used for HIFU procedures for pancreatic tumor pathology: generating ultrasonic waves of relatively high (5-20 kW/cm ² ) and low (less than 5 kW/cm ² ) intensity. The former are characterized by one or two procedures, the need for sedation or anesthesia, the patient's hospital stay, the risk of developing complications such as gastrointestinal bleeding and pancreatic fistula.

It is known to use high-energy devices (for example, JC HIFU system (Chongqing Haifu Tech Co. Ltd, Chongqing, China)) control of pain syndrome is achieved in 78.6-87.5%.

However, the authors of the article note the development of abdominal pain, fever and nausea in 28 (57.1%) cases after 49 HIFU ablation procedures, and among the complications of treatment - the development of skin burns of 2-3 degrees (4.1%), pancreatic fistula (4.1%), gastrointestinal bleeding (2.0%) (Sung H.Y., Jung S.E., Cho S.H., et al. Long-term outcome of high-intensity focused ultrasound in advanced pancreatic cancer. Pancreas. 2011;40 :1080-1086 Wang K, Chen Z, Meng Z, et al Analgesic effect of high intensity focused ultrasound therapy for unresectable pancreatic cancer Int J Hyperthermia 2011;27:101-107).

It is known to carry out relatively low-power HIFU therapy on the FEPBY02 HIFU system (Yuande Biomedical Engineering Co. Ltd, Beijing, China) with an ultrasonic flow intensity of 1 kW/cm ² , which makes it possible to achieve pain control in 80.6-92% of cases. The main exposure parameters were presented as follows: power 400-1000 W, insonation time - 150-200 ms, pause time - 150-200 seconds; processing time 30-50 seconds (75-125 pulses) at each point. The average number of treatment sessions was 1.2 per patient (range 1-2 sessions per patient); the average power was 586±78.4 W (Li PZ, Zhu SH, He W., et al. High-intensity focused ultrasound treatment for patients with unresectable pancreatic cancer. Hepatobiliary Pancreat Dis Int. 2012;11:655-660).

However, among the complications after ablation courses performed on this type of device, skin burns (3.4%), local sclerosis of subcutaneous adipose tissue (6.7%), development of asymptomatic pancreatic pseudocysts (1.1%) are noted (Xiong L.L., Hwang J.H., Huang X.B., et al.Early clinical experience using high intensity focused ultrasound for palliation of inoperable pancreatic cancer.JOP.2009;10:123-129).

It is known to conduct HIFU therapy on days 1, 3 and 5 of the course on the HIFUNIT-9000 device with an ultrasonic flow intensity of 3-8 kW/cm ² in parallel with MHT gemcitabine at a dosage of 1000 mg/m ² intravenously for 30 minutes at 1, 8 and Day 15 of a 28-day study in patients with locally advanced prostate cancer, which made it possible to achieve control of the level of tumor-mediated pain syndrome in 78.6% of patients.

However, when evaluating complications, 16.2% of patients had grade 3/4 neutropenia. Thrombocytopenia of the 3rd degree was registered in two (5.4%) patients. Nausea, grade 3 vomiting, and diarrhea were observed in three (8.1%) and two (5.4%) patients, respectively (Zhao H., Yang G., Wang D., et al. Concurrent gemcitabine and high-intensity focused ultrasound therapy in patients with locally advanced pancreatic cancer Anticancer Drugs 2010;21:447-452). This method did not take into account the variability in the size of the pancreatic tumor, which in patients with stage II can be up to 2 cm in diameter, and in patients with a locally advanced process - more than 8 cm.

The closest is the method of conducting HIFU therapy (Tao SF, Gu WH, Gu JC, et al. Focused ultrasound (HIFU) in combination with gemcitabine and oxaliplatin (gemox) on treating elderly middle and advanced pancreatic cancer. OncoTargets and Therapy. 2019; 12:9735-9745). Patients with stage II-IV prostate cancer undergo HIFU-therapy on the HIFUNIT-9000 device before starting chemotherapy in the GemOx mode. After this treatment, a statistically significant decrease in the level of abdominal pain syndrome was demonstrated from 5.86±2.13 points according to VAS to 2.03±0.51 (p<0.01). A decrease in the severity of pain syndrome was noted by 90.0% (27/30) of patients, a reduction in the dose of analgesics was observed in 76.6% (23/30) of patients. Ultrasound ablation was carried out with the following parameters: focal spot size - 3×3×8 mm, insonation time - 150-200 ms, interval time between pulses - 300-400 ms, number of pulses per treatment point - 8-14 times. The procedures were carried out once a day, in the amount of 5-16, the duration of treatment was 30-40 minutes. From the next day after completion of ablation, all patients started systemic chemotherapy in the GemOx regimen (gemcitabine 1000 mg/m ² on days 1 and 8 + oxaliplatin 135 mg/m ² on day 1 of a 21-day cycle). Each patient underwent at least 3 courses of chemotherapy. After the end of the HIFU procedure, mild pain in the right hypochondrium or lumbar region was noted in 3 (7.9%) patients; moderate and severe pain requiring the use of NSAIDs or morphine analgesics - 2 (5.2%) patients; fever up to 38.5°C lasting 1-3 days against the background of symptomatic treatment - 2 (5.2%) people. Obstructive jaundice developed in 2 (5.2%) patients with pancreatic head cancer after treatment. Toxic side effects of grade III-IV chemotherapy included leukopenia (18.4%), anemia (2.6%), thrombocytopenia (10.5%), hepatic hyperamylasemia (5.2%), nausea and vomiting (2.6%). %).

However, the use as a drug component of the GemOx regimen is not indicated for patients with impaired functional status corresponding to 2 points according to ECOG, this chemotherapy regimen has a significant spectrum of both hematological and non-hematological toxicity. Conducting HIFU-therapy on the device HIFUNIT-9000 with an ultrasonic flow intensity of 3-8 kW/cm ² demonstrated not quite satisfactory tolerance (development after the procedure of severe pain in the right hypochondrium or lumbar region (7.9%), moderate and severe pain, requiring the use of NSAIDs or morphine analgesics (5.2%), fever up to 38.5°C (5.2%), which, in patients with ECOG 2 status, would most likely be even worse.

The technical result of the invention is to increase the effectiveness of combined treatment, including chemotherapy and HIFU therapy, in the form of an increase in the frequency of pain syndrome control in patients with prostate cancer, who for one reason or another are not indicated for resection surgery, including somatically weakened patients with a functional status of ECOG 2.

The specified technical result in the implementation of the invention is achieved due to the fact that, just as in the known method, all patients receive a combination of systemic drug therapy with gemcitabine at a dosage of 750-1000 mg/m ² IV on the first, eighth and 15th days every 4 weeks with HIFU therapy.

A feature of the proposed method is that HIFU therapy sessions are carried out daily, except for the days of chemotherapy administration, on a low-energy apparatus with an ultrasonic flow intensity of 2 kW/cm ² , the number of pulses per point is 200, the pulse duration is 200 ms, the pause is 50 ms , the distance between the points along the x/y/z axes = 3/3/7 mm, and if the tumor size is:

- up to 2.0 cm, then for one course of HIFU therapy, 4 sessions are performed with an exposure duration of up to 30 minutes, or 3 sessions from 31 to 45 minutes, or 2 sessions from 46 to 60 minutes;

- from 2.1 to 4.0 cm, then for one course of HIFU therapy, 5 sessions are performed with an exposure duration of up to 30 minutes, or 4 sessions from 31 to 45 minutes, or 3 sessions from 46 to 60 minutes;

- from 4.1 to 6.0 cm, then for one course of HIFU therapy, 6 sessions are performed with an exposure duration of up to 30 minutes, or 5 sessions from 31 to 45 minutes, or 4 sessions from 46 to 60 minutes;

- from 6.1 to 8.0 cm, then for one course of HIFU therapy, 7 sessions are performed with an exposure duration of up to 30 minutes, or 6 sessions from 31 to 45 minutes, or 5 sessions from 46 to 60 minutes;

- if the size is more than 8.0 cm, then for one course of HIFU therapy, 8 sessions are performed with an exposure duration of up to 30 minutes, or 7 sessions from 31 to 45 minutes, or 6 sessions from 46 to 60 minutes. Treatment may be given to physically debilitated pancreatic cancer patients with an ECOG 2 functional status.

The acoustic power of the impact is selected individually, depending on the level of the patient's pain threshold. Moreover, this type of treatment can be indicated for somatically weakened patients with pancreatic cancer with a functional status of ECOG 2.

The method is carried out as follows.

Patients with prostate cancer with a functional status of ECOG 0-2, who are not indicated for radical surgical treatment, at the first stage of therapy, receive monochemotherapy (MCT) with gemcitabine at a dosage of 750-1000 mg/m2 IV in the 1st, 8th, 15th th days every 4 weeks in combination with HIFU therapy on a low-energy device with an ultrasound flow rate of 2 kW / cm ² (for example, HIFU-2001, Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) on an outpatient or inpatient basis. Before the start of each course, in order to minimize acoustic losses and prevent damage to the skin, the skin in the acoustic access zone is shaved, before the start of each session, it is treated with an alcohol-containing antiseptic. If necessary, cicatricial changes in the skin of the anterior abdominal wall were closed with air-containing polyethylene patches.

During the procedure, patients are placed on the table of the treatment and diagnostic module of the apparatus in the supination position in a tank with degassed water so that the tumor projection zone on the skin of the anterior abdominal wall is above the diagnostic sensor. The next step is to mark the tumor on the console of the apparatus under ultrasound guidance: select the amount of treatment, which was divided into horizontal layers, each of which is into impact points. Pointing the focus point of the emitters and selecting the exposure zone is carried out using a computer program (for example, HIFU-2001 Type High Intensity Focused Ultrasound Tumor Treatment System). Within 30-60 minutes (depending on the size of the tumor and the number of sessions planned), a pulsed high-intensity focused ultrasound effect on the tumor is performed in the marked volume. The procedure is carried out under ultrasound control (for example, on the apparatus Mindray DC-7, 2015). The power of exposure is selected individually depending on the level of the patient's pain threshold, by gradually increasing its level until subjective sensations appear.

After the end of exposure, the soft tissues of the acoustic window (primarily the skin and subcutaneous tissue) are visually, palpated and instrumentally (ultrasound) examined for the development of local reactions: skin burns, edema and thickening of the skin and subcutaneous fatty tissue. In the event of adverse events from healthy tissues in the affected area, ice was placed on this area for 15-20 minutes.

Sessions of HIFU-therapy are carried out daily (except for the days of chemotherapy administration) in the amount of 2-8 per course of therapy. The number of HIFU-therapy courses depends on the general functional status of the patient, tolerability of procedures, response of the tumor process to treatment according to control examinations. Local treatment is stopped if there is a marked deterioration in the general condition of the patient, corresponding to an ECOG score of 3, or the progression of the disease in the form of a clinically significant generalization of the process. The number of sessions for one course of local treatment is determined according to the developed matrix, depending on the maximum size of the planned treatment focus for 1 course and the level of tolerance of the procedure by the patient (the time during which the patient is able to be in a stationary position on the device without worsening general well-being) (table 1) . All sessions of HIFU therapy are carried out in the following mode: the number of pulses per point is 200, the pulse duration is 200 ms, the pause is 50 ms, the distance between the points along the x/y/z axes = 3/3/7 mm. The acoustic power of the impact is selected individually, depending on the level of the patient's pain threshold.

Table 1
Matrix for determining the required number of HIFU sessions Max. processing area size
Duration
impact up to 2 cm. 2-4 cm. 4-6 cm. 6-8 cm. over 8 cm. up to 30 min. 4 5 6 7 8 31-45 min. 3 4 5 6 7 46-60 min. 2 3 4 5 6

The study group included 29 (82.9%) women and 6 (17.1%) men, the average age of patients was 71.2±1.2 years. The inclusion criteria were: the presence of morphologically confirmed adenogenic PCa; instrumental signs of unresectable tumor, generalized process, or patients belonging to the category of functionally inoperable; functional status of patients ECOG ≤ 2; the presence of a clear visualization of the tumor with ultrasound marking on the HIFU-2001 device; the patient's ability to be immobile in the prone position during the HIFU procedure; the absence of previous RT, chemotherapy and/or other methods of local treatment of the pancreatic tumor; compensated concomitant somatic pathology; patient consent to participate in the study. Functional status corresponding to ECOG 0 was noted in 4 (11.4%) patients, ECOG 1 - in 12 (34.3%), ECOG 2 - in 19 (54.3%) patients. In 28 (80%) patients, the tumor was located in the head of the pancreas, in 6 (17.1%) - in the body, in 1 (2.9%) - in the tail of the organ. The spread of the tumor corresponding to stage IIA was detected in 5 (14.3%) patients, stage IIB - in 9 (25.7%), stage III - in 10 (28.6%), stage IV - in 11 (31 .4%) of patients. The maximum size of the tumor formation according to CT or MRI with intravenous contrast was in the range from 13 to 86 mm (mean - 43.6±1.8 mm). In 33 (94.3%) patients, there was a clinically-instrumental or laboratory confirmed comorbidity, in 30 (85.7%) cases - combined. Twenty-four (68.6%) patients at the start of treatment noted the presence of abdominal pain in the range from 3 to 9 points on the visual analog scale (VAS), the average value was 6.29±0.38.

All patients at the first stage of treatment underwent MCT with gemcitabine at a dosage of 750-1000 mg/m ² IV on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy. The median of MHT 1st line courses was 8 (range 3-12). Local therapy was performed on the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/cm2, in outpatient or inpatient mode, in the amount of 2-8 sessions per course with the following parameters: number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The acoustic power of the impact was selected individually, depending on the level of the pain threshold of the patient. Patients were excluded from the study if the disease progressed on the background of this treatment. With progression, in 20 (57.1%), the drug therapy regimen was changed to MCT with irinotecan (150-200 mg/m2 on day 1 of a 14-day cycle or 250-350 mg/ ^m2 on day 1 of a 21-day cycle ) or capecitabine (2000 mg/m2/day orally on days 1-14 every 3 weeks). Conducting HIFU exposure continued in the same volume. This therapy was implemented until the progression of the disease, the development of severe toxic complications, or a significant deterioration in the functional status of patients.

In the presence of persistent stabilization or partial response of the tumor at the end of 12 courses of combined treatment, patients were recommended to complete drug therapy until the disease progressed and continue HIFU therapy for 1 year in a regimen of 1 course (5 sessions) per month, monthly. In the absence of signs of disease progression after a year of HIFU monotherapy, the procedures were continued in the mode of 1 course (5 sessions) every 3 months.

As part of combination therapy, patients underwent 1422 HIFU sessions. The average number of HIFU-therapy courses per patient for the entire period of treatment was 8.9±1.0, the average number of sessions per course was 5.1±0.3, and the average exposure power was 511.7±12.2 W. The total duration of the procedure was in the range of 30-45 minutes, the median was 35 minutes.

The objective response rate (ORR) of the primary tumor site that underwent HIFU therapy after 3, 6, and 9 courses of combined treatment was 11.4%, 22.9%, and 22.9%, respectively. Local progression in these terms was noted in 2.9%, 8.6% and 14.3% of patients. The frequency of control of the primary tumor focus after 6 courses of therapy was 91.4%. The overall response of the tumor process to therapy at the time of the first three follow-up examinations of patients is presented in Table 2.

table 2
Distribution of patients depending on the overall response of the tumor process to combination therapy Assessment period
The nature of the response 3 courses
n(%) 6 courses,
n(%) 9 courses,
n(%) Partial answer 4 (11.4%) 5 (14.3%) 3 (8.6%) Stabilization 29 (82.9%) 19 (54.3%) 12 (34.3%) Progression 2 (5.7%) 11 (31.4%) 20 (57.1%)

The ORR of the tumor process at these temporary control points was 11.4%, 14.3%, 8.6%, respectively, the frequency of disease control was 94.3%, 68.6%, 42.9%. A decrease in the severity of the pain syndrome after 6 courses of treatment compared with the baseline was noted in 14 (58.3%) patients, the preservation of the severity of pain at the same level - in 9 (37.5%) patients, the increase in pain syndrome - in 1 (4 .2%) of the patient. The frequency of pain syndrome control was 95.8%. At the same time, a statistically significant decrease in the average level of pain syndrome according to VAS was revealed (6.29±0.38 versus 4.88±0.39, p = 0.001).

In 3 (0.2%) out of 1422 cases of HIFU therapy, the development of severe nausea was noted, which required interruption of the procedure. Complications of HIFU therapy were identified in 12 (34.3%) patients and represented by skin burns of 1-3 degrees (20%), obstructive jaundice (8.6%), development of reactive pancreatitis (8.6%), subcutaneous adipose sclerosis fiber (2.9%), the formation of pancreatic pseudocysts (2.9%). In 9 (25.7%) patients on the background of MCT with gemcitabine, toxic reactions of 3-4 degrees were detected, such as: neutropenia (14.3%), anemia (5.7%), thrombocytopenia (8.6%), growth liver transaminases (5.7%), diarrhea (2.9%).

Clinical examples of implementation.

Example #1.

Patient M., 76 years old, with a morphologically confirmed main clinical diagnosis of adenogenic pancreatic head cancer stage IIA cT3N0M0 and a functional status of ECOG 2, received 12 courses of combined treatment as the first line of therapy (MXT with gemcitabine 1000 mg/m ² iv in 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy on the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/ ^cm2 . The size of the tumor formation of the head of the pancreas at the time of treatment was 18×13×20 mm, the Patient complained of the presence of constant aching pain in the right hypochondrium, relieved by taking NSAIDs 1-2 times a day, the level of which was 4 points according to VAS. the treatment was carried out in a stationary mode, in the amount of 4 sessions per course with the following parameters: the number of pulses per point - 200, the pulse duration - 200 ms, the pause duration 50 ms, the distance between the points along the x/y/z axes = 3/3/ 7 mm. The duration of one session was in the range of 22-30 minutes due to the difficulty of the patient maintaining the desired body position on the device. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease according to RECIST 1.1 criteria was noted (the size of the tumor of the head of the pancreas was 16×15×18 mm, regional and distant metastatic foci were not detected), a decrease in the severity of pain syndrome to 1 point according to the VAS, contributing to the withdrawal NSAIDs. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 37 months, the time without disease progression was 12 months.

Example #2.

Patient P., 74 years old, with severe subcompensated cardiovascular comorbidity, which determines her functionally inoperable state, morphologically confirmed by the main clinical diagnosis "Adenogenic cancer of the body of the pancreas IIA stage cT3N0M0" and the functional status of ECOG 1, 9 courses were performed as the first line of therapy combined treatment (MXT with gemcitabine 750-1000 mg/m ² IV on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy using the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW / cm ^2. The size of the tumor of the body of the pancreas at the time of treatment was 20 × 10 × 12 mm At the time of treatment, the patient noted the presence of periodic unexpressed dull pain in the upper abdomen 2 points according to VAS, did not take painkillers.Local treatment was carried out on an outpatient basis, in the amount of 3 sessions per course with the following parameters: the number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along the x axes /y/z = 3/3/7 mm. The duration of one session was in the range of 31-45 minutes. When evaluating the effectiveness of therapy after 6 courses of treatment, a partial response was noted according to the RECIST 1.1 criteria (the size of the pancreatic head tumor was 13 × 7 × 10 mm, no regional and distant metastatic foci were detected), as well as complete relief of the pain syndrome. Among the toxic effects of gemcitabine grade 3-4, a single development of anemia was noted, which was the reason for reducing the dose of the cytostatic. After the 3rd course of combined treatment, the development of foci of local sclerosis of the subcutaneous adipose tissue in the area of the acoustic window (the epigastric region itself) was noted. The total life expectancy of the patient was 26 months, the time without disease progression was 9 months.

Example #3.

Patient K., 56 years old, with a morphologically confirmed main clinical diagnosis of "Adenogenic pancreatic head cancer stage IIA cT3N0M0" and a functional status of ECOG 1 due to a voluntary refusal to perform resection surgery as the first line of therapy, underwent 12 courses of combined treatment (MCT gemcitabine 1000 mg/m ² IV on days 1, 8, 15 every 4 weeks in combination with HIFU therapy using the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW / cm ^2. The size of the tumor formation of the head of the pancreas at the time of treatment was 15 × 10 × 12 mm The patient complained of the presence of dull pain in the epigastric region that occurs 1 hour after eating, stopped by taking NSAIDs 1 time per day, the level of which was 3 points according to VAS. With FEGDS, no data were obtained for the presence of acute pathology of the mucous membrane of the stomach and duodenum. Local treatment was carried out on an outpatient basis, in the amount of 2 sessions per course with the following parameters: the number of pulses in point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 46-60 minutes. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease was noted according to the RECIST 1.1 criteria - the size of the tumor of the pancreatic head was 15×8×10 mm, regional and distant metastatic foci were not detected. A moderate decrease in the severity of pain syndrome up to 2 points according to VAS was noted, which contributed to the preservation of the previous NSAID regimen. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 18 months, the time without disease progression was 12 months.

Example number 4.

Patient G., 79 years old, with a morphologically confirmed main clinical diagnosis of "Adenogenic cancer of the head of the pancreas IIB stage cT3N1M0" and a functional status of ECOG 2, 8 courses of combined treatment were performed as the first line of therapy (MCT with gemcitabine 750 mg/m ² iv in 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy on the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/ ^cm2 . The size of the tumor formation of the head of the pancreas at the time of treatment was 33×26×30 mm Before treatment, the patient noted constant aching pain in the upper abdomen, radiating to the left lumbar region, stopped by taking NSAIDs 3 times a day, the level of which was 5 points Local treatment was carried out in a stationary mode, in the amount of 5 sessions per course with the following parameters: the number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 25-30 minutes. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease according to RECIST 1.1 criteria was noted (the size of the tumor of the head of the pancreas was 31 × 25 × 30 mm, the preservation of regional lymphadenopathy in the same volume, the absence of distant metastases), a decrease in the severity of pain syndrome to 2 points according to VAS, contributing to a change in the regimen of NSAIDs up to 1 time per day. Grade 3-4 toxic effects of gemcitabine were not observed. After the 5th course of combined treatment, the development of a 1st degree skin burn in the acoustic access zone was noted. The total life expectancy of the patient was 16 months, the time without disease progression was 8 months.

Example number 5.

Patient Sh., 54 years old, with a morphologically confirmed main clinical diagnosis of adenogenic pancreatic head-body cancer stage IV cT3N1M1 (hep) and a functional status of ECOG 0, received 6 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² IVs on Days 1, 8, 15 every 4 weeks in combination with HIFU therapy using HIFU-2001 (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow rate of 2 kW / cm ^2. The size of the tumor formation of the head-body of the pancreas at the time of treatment was 35 × 34 × 38 mm Before treatment, the patient noted constant aching pain in the upper abdomen, aggravated after eating, stopped by taking tramadol 100 mg 2 times a day. day with additional intake of NSAIDs 1-2 times a day, the level of which was 7 points according to VAS Local treatment was carried out on an outpatient basis, in the amount of 4 sessions per course with the following parameters: the number of pulses per point - 200, the pulse duration - 200 ms , pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 31-45 minutes. When evaluating the effectiveness of therapy after 6 courses, progression of the disease according to the RECIST 1.1 criteria was noted in the form of the appearance of an additional tumor focus in the liver parenchyma 5 mm in size, the size of the primary tumor remained the same. Despite the progression of the disease, the patient noted a decrease in the severity of the pain syndrome to 4 points on the VAS, contributing to the abolition of the additional intake of NSAIDs. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 15 months, the time without disease progression was 6 months.

Example number 6.

Patient M., 77 years old, with a morphologically confirmed main clinical diagnosis of "Adenogenic cancer of the body of the pancreas IIB stage cT3N1M0" and a functional status of ECOG 2, received 8 courses of combined treatment as the first line of therapy (MXT with gemcitabine 1000 mg/m ² iv in 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy on the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/ ^cm2 . The size of the tumor formation of the body of the pancreas at the time of treatment was 40 × 28 × 37 mm Before treatment, the patient noted unexpressed pain in the right hypochondrium (VAS 2 points). parameters: number of pulses per point - 200, pulse duration - 200 msec, pause duration 50 msec, distance between points along the x/y/z axes = 3/3/7 mm Duration of one session was in the range of 46-60 minutes. When evaluating the effectiveness of therapy after 6 courses according to RECIST 1.1 criteria, the progression of the disease was noted in the form of the appearance of three small focal formations in the lung parenchyma up to 3 mm in size, the size of the primary tumor was 42 × 25 × 34 mm. The severity of the pain syndrome remained at the same level. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 14 months, the time without disease progression was 8 months.

Example number 7.

Patient M., 68 years old, with a morphologically confirmed main clinical diagnosis of "Adenogenic cancer of the head of the pancreas, stage V cT4N0M1(hep)" and a functional status of ECOG 2, 9 courses of combined treatment were performed as the first line of therapy (MCT with gemcitabine 750-1000 mg/m ² IVs on Days 1, 8, 15 every 4 weeks in combination with HIFU therapy using HIFU-2001 (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow rate of 2 kW / cm ^2. The size of the tumor formation of the pancreatic head at the time of treatment was 45 × 40 × 39 mm The patient noted the presence of constant moderate dull pain in the epigastric region, the level of which was 3 points according to VAS Local treatment was carried out in a stationary mode, in the volume of 6 sessions per course with the following parameters: the number of pulses per point - 200, the pulse duration - 200 ms, the pause duration 50 ms, the distance between the points along the x/y/z axes = 3/3/7 mm The duration of each session was 30 minutes. When evaluating the effectiveness of therapy after 6 courses of treatment, stabilization of the disease according to the RECIST 1.1 criteria (the size of the pancreatic head tumor was 46 × 42 × 35 mm), as well as the preservation of the severity of the pain syndrome at the same level, was noted. After the 3rd course of treatment, the development of neutropenia of the 3rd degree was noted, which was the reason for the reduction in the dose of the cytostatic. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 13 months, the time without disease progression was 9 months.

Example number 8.

Patient L., 77 years old, with a morphologically confirmed main clinical diagnosis of stage III adenogenic tail of the pancreas cancer cT4N0M0 and a functional status of ECOG 1, underwent 9 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² iv in 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy on the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/ ^cm2 . The size of the tumor formation of the head of the pancreas at the start of treatment was 48×35×44 mm.Before treatment, the patient complained of the presence of periodic pulling pain in the upper abdomen with an intensity of up to 7 points according to VAS at night.For the purpose of pain relief, he took tramadol 100mg in the evening, NSAIDs 3 times a day.Local treatment was carried out on an outpatient basis, in the amount of 5 sessions per course with the following parameters: the number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along the x axes /y/z = 3/3/7. The duration of the HIFU-therapy session was 31-45 minutes. When evaluating the effectiveness of therapy after 6 courses of combination therapy, tumor stabilization was noted according to RECIST 1.1 criteria with a decrease in its maximum size by 21% (up to 38×32×36 mm) and a decrease in the severity of pain syndrome to 3 points according to VAS, against which the patient began to take tramadol 100 mg once a day and NSAIDs once a day. Grade 3-4 toxic effects of gemcitabine were not observed. After the 6th course of combined treatment, the development of local sclerosis of the subcutaneous adipose tissue of the left hypochondrium was noted. The total life expectancy of the patient was 19 months, the time without disease progression was 9 months.

Example #9.

Patient D,, aged 67, with a morphologically confirmed main clinical diagnosis of "Adenogenic cancer of the body of the pancreas, stage III cT4N1M0" and a functional status of ECOG 2, received 12 courses of combined treatment as the first line of therapy (MCT with gemcitabine 750-1000 mg/m ² i.v.). c on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy using the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/cm ^2. The size of the tumor formation of the body of the pancreas at the time of treatment was 56 × 42 × 40 mm Prior to treatment, the patient noted the presence of severe constant pulling pain in the upper abdomen with an intensity of 7 points according to VAS. day, NSAIDs 1-3 times a day.Local treatment was carried out in a stationary mode, in the amount of 4 sessions per course with the following parameters: the number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along axes x/y/z = 3/3/7. The duration of the HIFU-therapy session was 46-60 minutes. When evaluating the effectiveness of therapy after 6 courses of treatment, a partial response of the tumor was noted according to the RECIST 1.1 criteria (reduction in the size of the primary focus to 35 × 29 × 30 mm) and a decrease in the severity of the pain syndrome to 4 points according to the VAS, against which the patient stopped taking tramadol and took only NSAIDs 2 times a day. After the 4th course of combined treatment, the development of thrombocytopenia of the 3rd degree was noted, and therefore the dose of gemcitabine was reduced to 750 mg/m ² . Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 38 months, the time without disease progression was 24 months.

Example number 10.

Patient M., 77 years old, with a morphologically confirmed main clinical diagnosis of stage III adenogenic cancer of the body-tail of the pancreas cT4N1M0 and a functional status of ECOG 1, received 7 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² i.v. c on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy using the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/cm ^2. The size of the tumor formation of the body-tail of the pancreas at the start of treatment was 68 × 50 × 44 mm Before treatment, the patient noted the presence of unexpressed periodic pain in the epigastric region with an intensity of 3 points according to VAS. He took NSAIDs 1-2 times a day. Local the treatment was carried out in a stationary mode, in the amount of 7 sessions per course with the following parameters: the number of pulses per point - 200, the pulse duration - 200 ms, the pause duration 50 ms, the distance between the points along the x/y/z axes = 3/3/ 7. The duration of the HIFU-therapy session was 24-30 minutes. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease according to the RECIST 1.1 criteria (tumor size was 64×52×40 mm) and an unexpressed decrease in the severity of pain syndrome to 2 points according to VAS were noted. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 13 months, the time without disease progression was 7 months.

Example number 11.

Patient B., 73 years old, with a morphologically confirmed main clinical diagnosis of adenogenic pancreatic head-body cancer stage IV cT4N1M1(hep) and a functional status of ECOG 1, received 6 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² IVs on Days 1, 8, 15 every 4 weeks in combination with HIFU therapy using HIFU-2001 (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow rate of 2 kW / cm ^2. The size of the tumor formation of the head-body of the pancreas at the time of treatment was 63×48×52 mm The patient complained of the presence of constant aching pain in the right hypochondrium, stopped by taking NSAIDs 2 times a day, the level of which was 5 points according to VAS Local treatment was carried out on an outpatient basis, in the amount of 6 sessions per course with the following parameters: the number of pulses per point - 200, the pulse duration - 200 ms, the pause duration 50 ms, the distance between the points along the x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 31-45 minutes. When evaluating the effectiveness of therapy after 6 courses, progression of the disease according to the RECIST 1.1 criteria was noted in the form of the appearance of an additional focal formation in the liver parenchyma measuring 11 × 7 mm, while the size of the pancreatic head tumor was 62 × 45 × 50 mm; decrease in the severity of pain syndrome to 3 points according to VAS, which helps to reduce the frequency of taking NSAIDs to 1 time per day. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 10 months, the time without disease progression was 6 months.

Example No. 12.

Patient V., 69 years old, with a morphologically confirmed main clinical diagnosis of "adenogenic pancreatic head cancer stage IV cT4N1M1(hep, lnn)" and a functional status of ECOG 0, received 12 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² IVs on Days 1, 8, 15 every 4 weeks in combination with HIFU therapy using HIFU-2001 (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow rate of 2 kW / cm ^2. The size of the tumor formation of the pancreatic head at the time of treatment was 46×39×65 mm. The patient complained of unexpressed periodic pain in the central abdomen (VAS 2 points), did not take painkillers. Local treatment was carried out in outpatient mode, in the amount of 5 sessions per course with the following parameters: number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 46-60 minutes. When evaluating the effectiveness of therapy after 6 courses, a partial response of the tumor according to the RECIST 1.1 criteria was noted (the size of the tumor of the head of the pancreas was 35 × 29 × 37 mm, with no signs of the appearance of new regional or distant focal formations) and complete relief of the pain syndrome, which made it possible to stop taking NSAIDs. Grade 3-4 toxic effects of gemcitabine were not observed. After the 2nd course of HIFU therapy, a 1st degree skin burn developed in the right hypochondrium. The total life expectancy of the patient was 31 months, the time without disease progression was 17 months.

Example No. 13.

Patient Ya., 67 years old, with a morphologically confirmed main clinical diagnosis of stage IV adenogenic tail of the pancreas cancer cT3N1M1(hep) and a functional status of ECOG 1, received 6 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² in /v on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy using the HIFU-2001 device (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow intensity of 2 kW/ cm ^2. The size of the tumor formation of the tail of the pancreas at the time of treatment was 82×61×69 mm Before therapy, the patient complained of moderate periodic aching pain in the left hypochondrium and lumbar regions (VAS 4 points), took NSAIDs 1-2 times Local treatment was carried out on an outpatient basis, in the amount of 8 sessions per course with the following parameters: the number of pulses per point - 200, pulse duration - 200 ms, pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 22-30 minutes. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease according to the RECIST 1.1 criteria was noted - without dynamics in the size of the primary tumor and the appearance of new metastases. The severity of the pain syndrome remained at the same level. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 9 months, the time without disease progression was 7 months.

Example No. 14.

Patient M., 54 years old, with a morphologically confirmed main clinical diagnosis of "Adenogenic cancer of the body-tail of the pancreas, stage IV cT4N0M1(hep)" and a functional status of ECOG 1, 9 courses of combined treatment were performed as the first line of therapy (MCT with gemcitabine 1000 mg/m ² IVs on Days 1, 8, 15 every 4 weeks in combination with HIFU therapy using HIFU-2001 (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow rate of 2 kW / cm ^2. The size of the tumor formation of the body-tail of the pancreas at the time of treatment was 86 × 55 × 67 mm Before therapy, the patient complained of severe constant aching pain in the upper abdomen, aggravated at night (VAS 8 points), for the purpose of anesthesia, a transdermal patch with fentanyl, tramadol 50 mg up to 2 times a day, NSAIDs 1-2 times a day was used.Local treatment was carried out on an outpatient basis, in the amount of 7 sessions per course with the following parameters: the number of pulses per point - 200 pulse duration - 200 ms, pause duration 50 ms, distance between points along x/y/z axes = 3/3/7 mm. The duration of one session was in the range of 31-45 minutes. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease according to the RECIST 1.1 criteria, a decrease in the severity of pain syndrome to 6 points according to VAS with the continuation of analgesic drug therapy in the same volume were noted. Grade 3-4 toxic effects of gemcitabine were not observed. After the 3rd course of combined treatment, focal sclerosis of the subcutaneous adipose tissue in the area of acoustic access was noted. The total life expectancy of the patient was 17 months, the time without disease progression was 12 months.

Example #15.

Patient A., 59 years old, with a morphologically confirmed main clinical diagnosis of stage IV adenogenic tail of the pancreas cancer cT4N1M1(hep, pulm) and a functional status of ECOG 2, received 6 courses of combined treatment as the first line of therapy (MCT with gemcitabine 1000 mg/m ² IVs on Days 1, 8, 15 every 4 weeks in combination with HIFU therapy using HIFU-2001 (Shenzhen Huikang Medical Apparatus Co., LTD, China, 2015) with an ultrasonic flow rate of 2 kW / cm ^2. The size of the tumor formation of the tail of the pancreas at the time of treatment was 84×62×65 mm Before therapy, the patient complained of moderate dull pain in the left hypochondrium (VAS 5 points), took NSAIDs 1-2 times a day Local treatment was carried out in a stationary mode, in the amount of 6 sessions per course with the following parameters: the number of pulses per point - 200, the pulse duration - 200 ms, the pause duration 50 ms, the distance between the points along the x/y/z axes = 3 /3/7 mm. The duration of one session was in the range of 46-60 minutes. When evaluating the effectiveness of therapy after 6 courses, stabilization of the disease according to the RECIST 1.1 criteria was noted (the size of the primary tumor was 81 × 60 × 58 mm), maintaining the level of pain syndrome severity with the continuation of analgesic drug therapy in the same volume. Grade 3-4 toxic effects of gemcitabine were not observed. Complications of HIFU therapy have not been identified. The total life expectancy of the patient was 11 months, the time without disease progression was 8 months.

The use of this invention will increase the frequency of pain syndrome control (reducing its severity or maintaining it at the same level) already after 6 months of combination therapy, by achieving stabilization and/or partial response of the primary focus, a low degree of cytostatic toxicity and the absence of a negative effect of treatment on functional the status of the patients. The use of this method will expand the possibilities of antitumor and analgesic therapy by including patients with a weakened functional status corresponding to ECOG 2.

Claims (6)

A method for reducing the severity of chronic pain in patients with pancreatic cancer with a functional status of ECOG 0-2 points, including courses of monochemotherapy with gemcitabine at a dosage of 750-1000 mg/m ² IV on the 1st, 8th, 15th days every 4 weeks in combination with HIFU therapy, characterized in that HIFU therapy sessions are carried out daily, except for the days of chemotherapy administration, on a low-energy device with an ultrasound flow intensity of 2 kW / cm ² , the number of pulses per point - 200, the pulse duration - 200 ms, pause duration 50 ms, distance between points along the x/y/z axes = 3/3/7 mm, and if the tumor size is: - up to 2.0 cm, then for one course of HIFU therapy, 4 sessions are performed with an exposure duration of up to 30 minutes, or 3 sessions from 31 to 45 minutes, or 2 sessions from 46 to 60 minutes; - from 2.1 to 4.0 cm, then for one course of HIFU therapy, 5 sessions are performed with an exposure duration of up to 30 minutes, or 4 sessions from 31 to 45 minutes, or 3 sessions from 46 to 60 minutes; - from 4.1 to 6.0 cm, then for one course of HIFU therapy, 6 sessions are performed with an exposure duration of up to 30 minutes, or 5 sessions from 31 to 45 minutes, or 4 sessions from 46 to 60 minutes; - from 6.1 to 8.0 cm, then for one course of HIFU therapy, 7 sessions are performed with an exposure duration of up to 30 minutes, or 6 sessions from 31 to 45 minutes, or 5 sessions from 46 to 60 minutes; - if the size is more than 8.0 cm, then for one course of HIFU therapy, 8 sessions are performed with an exposure duration of up to 30 minutes, or 7 sessions from 31 to 45 minutes, or 6 sessions from 46 to 60 minutes.