RU2806105C1 - Method of choosing tactics for postoperative treatment of medullary thyroid cancer - Google Patents

Abstract

FIELD: medicine; oncology.

SUBSTANCE: invention can be used to select tactics for postoperative treatment of medullary thyroid cancer. The method includes determining the level of calcitonin (CT) in the blood after radical thyroidectomy and lymphadenectomy, using drug therapy taking into account the level of the CT value. If a CT value of > 150 pg/ml is detected, vandetanib is administered orally at a daily dose of 200 mg for 12 months. If a blood CT value is detected in the range of 100–150 pg/ml, external beam radiation therapy is applied to the area of the bed of the removed thyroid gland in the average fractionation mode ROD-3.5 Gy to 35 Gy, and to the area of groups of lymph nodes II–IV, VI in the average mode fractionation ROD-3.5 Gy to SOD – 42 Gy.

EFFECT: use of the invention makes it possible to achieve a reduction in the risk of locoregional relapse, increase the comfort of life, increase relapse-free survival in patients with MTC, reduce the risks of complications due to personalized prescription of drug or radiation therapy, correct determination of groups of neck lymph nodes included in the radiation target, determination of the most effective radiation therapy regimen.

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Description

The invention relates to medicine, namely to oncology, and can be used in the postoperative treatment of medullary thyroid cancer (MTC).

There is a known method for choosing treatment for medullary thyroid cancer in the postoperative period (Skvortsov V.V., Vlasov M.Yu. Medullary thyroid cancer. Features of diagnosis and treatment. "Povolzhsky Oncological Bulletin". No. 2(34) 2018), p. 24-28) To determine the tactics of patient management in the postoperative period, the following is used: postoperative risk stratification taking into account the TNM stage, the level of basal calcitonin (CT) and in the absence of biochemical remission - assessment of the doubling time of the basal CT level. After surgery, the level of calcitonin in the blood is assessed after 3 months. If the calcitonin level is more than 150 pg/ml, additional examinations are performed including ultrasound of the neck (CT of the neck), CT of the chest and abdominal organs, bone scintigraphy, MRI of the bones of the spine and pelvis. Only if locoregional relapse or distant metastases are detected, surgical treatment or radiation therapy is prescribed. If a widespread process is identified, targeted therapy is indicated. In the postoperative period, radiation therapy is possible in the case of non-radical surgery and if a large number of lymphatic metastases are detected. The irradiation zone includes the area of the thyroid gland bed and the area of the lateral lymph nodes of the neck. The total radiation dose is 44-60 Gy.

The disadvantages of this method are the wait-and-see tactics of postoperative management of patients with MTC, regardless of the postoperative blood CT level, which creates conditions for more intense tumor progression, the lack of clear criteria for adjuvant radiation therapy, including its regimen and target volume, and the use of proven drugs itself as an effective treatment for MTC.

The closest is the method of choosing tactics for postoperative treatment of medullary thyroid cancer with octreotide - depot (RF Patent 2403914, IPC A61K 38/31, A61R 35/00). The method includes determining the level of calcitonin (CT) in the blood before and after surgery, as well as immunohistochemical examination of the surgical material. Depending on the CT level within 3 months after surgery and the proliferative activity of cells, a treatment regimen with octreotide depot is determined.

The disadvantages of this method are the prescription of drug therapy based on data on the direction of the dynamics of changes in the blood CT value in the postoperative period and the CT value immediately after surgery is not taken into account, the relationship between the risk of distant metastasis and the blood CT value in the postoperative period is not taken into account, low efficiency is not taken into account octreodite is a depot in such patients, combined with the likelihood of complications when taking it, the radicalism of the surgical intervention performed, and the refusal to use radiation therapy as an effective means of treating MTC are not taken into account.

The objective of the present invention is to reduce the risk of locoregional relapse, increase the comfort of life, increase relapse-free survival in patients with MTC, reduce the risk of complications, by eliminating these shortcomings by personalized prescription of drug or radiation therapy, correct determination of groups of neck lymph nodes included in the radiation target, determining the most effective radiation therapy regimen.

The method includes determining the blood CT calcitonin level after radical thyroidectomy and lymphadenectomy, using drug therapy taking into account the CT value level. What is new is that if a CT value of >150 pg/ml is detected, vandetanib is used orally at a daily dose of 200 mg for 12 months; if a blood CT value is detected within 100 pg/ml - 150 pg/ml, external beam radiation therapy is used to the bed area the removed thyroid gland in the mode of average fractionation ROD-3.5 Gy to 35 Gy, and in the area of groups of lymph nodes II-IV, VI in the mode of average fractionation ROD-3.5 Gy to SOD - 42 Gy.

The technical result of using the proposed method is to reduce the risk of developing locoregional and distant relapse, reducing the toxicity of postoperative radiation or drug therapy.

The implementation of the method is shown in specific clinical examples.

Example 1.

Patient Sh. 51 years old. The patient consulted a doctor with complaints of the appearance of a tumor-like formation on the anterior surface of the lower third of the neck. During the examination, including ultrasound of the soft tissues of the neck and puncture biopsy, it was determined that there was a tumor up to 2.5 cm in diameter of the left lobe of the thyroid gland, which did not extend to the capsule. No enlargement of more than 1 cm of lymph nodes in the neck was detected. After a puncture biopsy, T2N0 MTC was diagnosed. The blood calcitonin level in the preoperative period was 856 pg/ml.

The patient underwent radical thyroidectomy with central lymph node dissection (lymph node group VI) - the diagnosis was fully confirmed - T2N1a. In the postoperative period, the blood calcitonin level was 202 pg/ml. The examination did not reveal evidence of local or distant metastasis. The patient was prescribed vandetanib at a daily dose of 200 mg, treatment with which lasted 12 months.

18 months after surgical treatment, no signs of progression of MTC were found.

Example 2.

Patient A. 62 years old. She contacted an endocrinologist with complaints about a tumor formation in the thyroid gland. The blood calcitonin level was 1259 pg/ml. After examination, T1N0 MTC was diagnosed.

The patient underwent total thyroidectomy and central lymph node dissection. One lymphogenous metastasis was detected in the paratracheal zone, which did not extend beyond the border of the lymph node capsule. The patient underwent a CT blood level test 3 weeks after surgery - 132 pg/ml.

Taking into account the obtained data, the patient received a course of adjuvant radiation therapy using the IMRT technique in the ROD 3.5 Gy up to 35 Gy to the area of the removed tumor bed and the area of group II-IV and VI lymph nodes in the ROD 3.5 Gy up to 42 Gy.

12 months after completion of radiation therapy, examination revealed no evidence of progression or complications.

Example 3

Patient Sh. is 51 years old. Total thyroidectomy and central lymph node dissection were performed for T2H1a medullary thyroid cancer. When examining the blood CT level in the postoperative period, it was found that it was 100 pg/ml.

The patient received a course of adjuvant radiation therapy using the IMRT technique in the ROD mode of 3.5 Gy up to 35 Gy and on the area of the removed tumor bed and the area of the lymph nodes, groups II-IV and VI up to 42 Gy.

16 months after completion of radiation therapy, examination revealed no evidence of progression or complications.

Example 4

Patient X., 45 years old, underwent total thyroidectomy and central lymph node dissection for T2N0 medullary thyroid cancer. When examining the blood CT level in the postoperative period, it was found that it was 150 pg/ml.

The patient underwent a course of adjuvant (postoperative) radiation therapy using the IMRT technique in the ROD mode of 3.5 Gy up to 35 Gy and 42 Gy to the area of the removed tumor bed and the area of the lymph nodes (groups II-IV and VI), respectively.

After 20 months from the date of surgery, no evidence of progression or complications was identified.

The method was used when prescribing postoperative treatment in 17 patients with medullary thyroid cancer. There were no serious complications (toxicity) associated with the administration of radiation or drug therapy that had a long-term negative impact on the functional state of patients, requiring the inclusion of additional volumes of medical care in the treatment regimen for such patients. The median duration of follow-up for patients from the moment of surgical intervention is 13 months. According to the results of the latest clinical examination, no signs of locoregional or distant metastasis were found in all of the above patients.

The proposed method for the first time, based on the results of a postoperative CT study, allows you to individually assess the risks of locoregional or distant metastasis in medullary thyroid cancer and, based on the data obtained, use the most effective treatment tactics, including either radiation therapy in a hypofractionated mode or drug therapy, including the use of a modern inhibitor tyrosine kinases. This approach simultaneously provides both an increase in relapse-free survival and high comfort of life by reducing the incidence of complications associated with the prescribed treatment.

Claims (1)

A method for selecting tactics for postoperative treatment of medullary thyroid cancer T1-2N0-1a, including determining the level of calcitonin on a blood CT scan after radical thyroidectomy and lymphadenectomy, the use of drug therapy taking into account the level of the CT value, characterized in that when a CT value of >150 pg/ml is detected, it is used vandetanib orally in a daily dose of 200 mg for 12 months, if a blood CT value is detected within 100-150 pg/ml, external beam radiation therapy is used on the area of the bed of the removed thyroid gland in the mode of average fractionation ROD-3.5 Gy to 35 Gy, and to the area of groups of lymph nodes II-IV, VI in the average fractionation mode ROD-3.5 Gy to SOD - 42 Gy.