Combined method for treating locally disseminated forms of thyroid gland carcinoma and its recurrences

FIELD: medicine.

SUBSTANCE: method involves applying intraoperative radiation therapy with rapid electrons of 6 MeV with single dose of 8 Gray per removed tumor bed. Then, postoperative remote gamma-therapy course is applied after having healed the wound and removing sutures to postoperative suture region and regional lymph discharge zone at a dose of 2 Gray with 5 fractions per week. The number of remote gamma-therapy sessions is calculated from formula N=8.8(3.4-X-0.169), where N is the number of postoperative remote gamma-therapy sessions; X is the time interval length in days between the intraoperative radiation therapy session and remote gamma-therapy session under condition that mixed irradiation dose (intraoperative radiation therapy and remote gamma-therapy) to thyroid gland tumor region or cancer recurrence area is equal to 60 Gray in terms of isoeffect.

EFFECT: increased total course dose per tumor focus; reduced risk of relapse; accelerated treatment course.

1 tbl

 

The invention relates to medicine, namely to Oncology, and can be used in the combined treatment of locally advanced common forms, ineradicable operated and recurrence of well-differentiated forms of thyroid cancer (thyroid cancer).

There is a method of treatment of differentiated forms and recurrence of thyroid cancer surgery, which is essential in the treatment of malignant tumors of the thyroid gland (analog) [3].

The disadvantage of this method is:

- the possibility of recurrence of thyroid cancer after surgery, as in 65.4% of cases [2] patients are found remains of the tumor tissue, resulting in continued tumor growth;

- risk of metastasis during or after surgery, as around the capsule of the thyroid gland expressed a network of lymphatic vessels [3], which may contribute to the spread of metastases during surgery.

Known combined method of treatment of cancer of the mucous membrane of the floor of mouth with the use of intraoperative radiation therapy (IORT) [4]. Intraoperative radiation therapy was not carried out in the combined treatment of thyroid cancer and its recurrence.

In the treatment by known methods of differentiated forms of thyroid cancer and its recurrence has the following disadvantages:

when surgical treatment differences the bathrooms forms of thyroid cancer or its recurrence in more than 50% of cases remain the microsections tumor tissue [2];

- during surgery can occur proliferation of tumor cells through the lymphatic ducts, due to the delayed application of the postoperative course of gamma therapy in SOD 40 Gy;

- due to the resistance of differentiated forms of thyroid cancer and its recurrence to photon radiation total focal dose of 40 Gy is insufficient;

- increase dose rate of postoperative rate of photon therapy to SOD - 60 Gy radiation increases the load on the spinal cord;

- combined treatment with IORT with thyroid cancer or its recurrence has not previously been used.

There is a method of combined treatment of locally common forms of cancer and recurrence of thyroid cancer with postoperative course of gamma-therapy on the area of the removed tumor and the area of regional lymph flow in standard mode: single focal dose of 2.0 Gy, 5 fractions per week to a total focal dose (SOD) - 40 Gy to the area of the removed tumor and areas of regional lymph (prototype) [1].

The disadvantage of this method is:

- during the operation fails exposure "box" removed tumor that may spread remaining microfocused tumor tissues through the lymphatic ducts;

- rate remote gamma-therapy in standard mode fractionation dose starts after the healing of postoperative wounds and SN is ment seams and lasts for 4-5 weeks;

- due to the resistance of differentiated forms of thyroid cancer, especially cancer recurrence to photon radiation total focal dose of 40 Gy of postoperative radiation therapy is insufficient;

- increase dose postoperative course until SOD 60 Gy, as with the radical program, increases the radiation dose to critical organs, in particular, on the spinal cord.

The task of the invention is to increase the effectiveness of treatment of locally common forms, ineradicable operated and recurrence of well-differentiated forms of thyroid cancer by increasing the total dose rate at the center target ("bed" of the removed tumor), reducing the number of relapses, prevent the spread of the remaining microfocused tumor tissues through the lymph system, the reduction of treatment time due to the use of radiation during surgery fast 6 MeV electrons with a single dose of 8 Gy and followed by postoperative remote gamma-therapy in standard mode on the hearth-target and area regional lymph flow.

This object is achieved in that in the conditions of the combined treatment of well-differentiated cancer or recurrence of thyroid cancer on the hearth-target spend intraoperative radiation therapy fast electron average energy of 6 MeV once the dose of 8 Gy. After the healing of postoperative wounds and removing operating seams spend postoperative remote gamma-therapy in standard mode fractionation ROD 2.0 Gy, 5 times a week on the area of the postoperative scar and the area of regional lymphatic drainage. The calculation of the number of sessions postoperative DHT is conducted according to the formula:

where N is the number of sessions postoperative DHT, X is the time interval in days between session IORT and DHT, provided that the dose of mixed irradiation (IORT and DHT) on the area of the removed tumor of the thyroid gland or cancer recurrence is for the treatment of 60 Gy in isoeffective, or 100 usled

Formula (1) was obtained based on the known formula [5]:

In the formula (2) WDF - factor Time-Dose-Fractionation, Du, Xu- single dose of IORT in Gr and the time interval in days between session IORT and DHT, respectively; Df,iand Xf,i- single dose of DHT in Gr and the time interval in days between sessions DHT; N - number of sessions DHT [5].

If the formula (2) to Express explicitly the number of radiation sessions N for specific values included in (2) parameters, we can obtain the formula (1).

The proposed method of treatment is carried out as follows. During the operation, after removal of the residual (after PE the primary non-radical surgery) or recurrent tumors in well-differentiated thyroid cancer in the area focus target spend intraoperative radiation therapy fast 6 MeV electrons from one, rarely (if necessary) with two beams size 6x6 cm, or 7×11 see a Single dose of IORT - 8 Gr down for each irradiation field. The value of a single dose of IORT - 8 Gr selected after clinical testing of combined treatment and analysis of its results in patients with thyroid cancer. After healing of wounds and the removal of the stitches on the area of focus target and regional lymph flow (the area of the cervical lymph nodes) conduct remote gamma-therapy with one field exposure size 10-12×20-22 cm in standard mode fractionation dose: ROD 2.0 Gy, 5 fractions per week. The magnitude of the number of sessions postoperative DHT calculated according to the formula N=8,9(3,4-X-0,169), where N is the number of sessions postoperative DHT, X is the time interval in days between session IORT and DHT, provided that the dose of mixed irradiation (IORT and DHT) on the area of the removed tumor of the thyroid gland or cancer recurrence is for the treatment of 60 Gy in isoeffective, or 100 srvc. ed WDF.

Critical organs larynx, trachea - escaped lead blocks after reaching SOD remote gamma-therapy 20 Gy, which reduces radiation exposure by 20% and reduces the possibility of radiation reactions and remote radiation damage vital critical organs.

Required when carrying out the proposed method is that the course is the first dose in the center of the target should be 60 Gy (100 srvc. ed WDF)that does not exceed the established tolerance for normal tissues.

New in the proposed method is that during the operation used intraoperative radiation therapy (IORT) - 8 Grams of fast electrons average energy of 6 MeV at the center target, and after surgery and removal of sutures undergo remote gamma-therapy on the hearth-target and area of lymphatic drainage, while the calculation of the number of sessions postoperative DHT is conducted according to the formula:

N=8,9(3,4-X-0,169),

where N is the number of sessions postoperative DHT, X is the time interval in days between session IORT and DHT, provided that the dose of mixed irradiation (IORT and DHT) on the area of the removed tumor of the thyroid gland or cancer recurrence is for the treatment of 60 Gy in isoeffective, or 100 used WDF.

Conducted clinical testing tolerability of a single dose of IORT in patients with thyroid cancer after non-radical surgery and recurrence of thyroid cancer showed that a dose of 8 Gy is well tolerated by patients, complications were observed in only one case (4%) of 24 patients in the form of edema from the mucosa of the trachea, which were stopped by means of medication during the day. To prevent swelling of the mucous membrane of the trachea in the following, all patients in the nearest postoperative period prescribed drug therapy, resulting in such complications in the future not OBS is given in any case. Used a beam of fast electrons average energy of 6 MeV has a limited mileage of fast electrons in the tissue, the 80% isodose curve, which is calculated doses, is located at a depth of 1.7 cm from the surface of the field of irradiation, which also contributes to sparing the mucosa of the trachea and larynx.

Thus, in the combined treatment of locally advanced common forms, ineradicable operated and recurrence of well-differentiated forms of thyroid cancer (thyroid cancer) radiation therapy mixed irradiation (IORT and DHT) is performed under the control of the assessment of biological effects indicators factor WDF, while the total course dose of 60 Gy in isoeffective, and the factor of WDF is 100 srvc. units

The proposed method were treated 24 patients with differentiated forms ineradicable operated cancer and recurrent thyroid cancer. Of the 24 patients, only one (4%) patient was observed in mild edema of the mucosa of the trachea and larynx in the immediate postoperative period. Other complications and radiation damage in the remote period of observation in patients with thyroid cancer was not observed after conducting a combined treatment with IORT a single dose of 8 Gy and remote gamma-therapy to SOD 60 Gr. The characteristic indicators of the rate of mixed irradiation (IORT and DHT) in patients with diff is linzirovannye forms of thyroid cancer and observed during the course of DHT in the form of light radiation reaction are presented in table 1.

Here is additional clinical examples:

Example 1. Patient A., 53, case History No. 118075. Diagnosis: thyroid Cancer T3N0M0condition after non-radical surgery. Continued growth. Histology: follicular cancer. In the hospital oncological profile performed surgery in the amount of resection of the left lobe of the thyroid gland about the alleged nodular goiter. At Oncology research Institute conducted reoperate in the amount of thyroidectomy (removal of the remnants of the thyroid gland) with IORT, GENUS 8,0 Gr a single field. The postoperative period was uneventful wound healing by primary intention, the sutures were removed on the 7th day. On the ninth day after the operation started, the rate of postoperative gamma therapy conducted to SOD 60 Gr. The calculation of the number of sessions postoperative gamma therapy carried out according to the formula:

N=8,9(3,4-X-0,169), where N is the number of sessions postoperative DHT, X is the time interval in days between session IORT and DHT. The value of N was 24 session.

Considering the magnitude of the GENUS IORT-8,0 G, the duration of the postoperative period until the early postoperative radiotherapy course is 9 days and the amount of DHT was 48 Gy to a total dose rate of 60 Gy (100 srvc. ed WDF) isoeffective that does not exceed the tolerance of normal tissues. The terms dynamic follow-up was 8 years old. P and dynamic monitoring data for recurrence, metastasis is not received.

Example 2. Patient U., 21, case History No. 121147. Was in OOGS with 22.11.99 on 17.02.00. Diagnosis: thyroid Cancer T3N0M0condition after non-radical surgery. In General physicians about the alleged nodular goiter performed Subtotal resection of the thyroid gland in Nikolaev. Histology: follicular cancer. At Oncology research Institute performed the surgery: Thyroidectomy (removal of the thyroid gland), IORT - 8 Gy in "bed" of the right lobe. Postoperative paresis of the right recurrent nerve, light swelling of the mucous membrane of the larynx and upper divisions of the trachea. Healing by primary intention. On the 14th day started the postoperative course of radiation gamma therapy. Held 25 sessions DHT (50 Gy) to dose rate of SOD - 60 Gr. The observation period is 4.5 years. For dynamic monitoring data for recurrence, metastasis is not received.

Thus, the proposed set of distinctive features has resulted in a new unknown early positive effect, which consists in increasing the effectiveness of treatment and reducing treatment time, reducing the number of relapses.

Table 1
№ p/pThe patient's age, no East. diseaseMor is ideological diagnosis Indications for surgery with IORT and DHT in patients with thyroid cancerSingle focal dose IORTTime interval (days) DHTTgthr (number of sessions)CD (G)Radiation reaction
1.A., 53, No. 118075Follicular thyroid cancerResidual tumor after non-radical surgery.8,0 Gr948 Gy (24th session)60Catarrhal laryngitis
2.U., 21, No. 121147Follicular thyroid cancerContinued tumor growth8,0 Gr1450 G (25 sessions)60Dry epidermis
*KD - dose rate of the mixed radiation.

Sources of information

1. Pačes A.I. of head and neck Tumors - M - 1997, - 479 S. (prototype).

2. Birzu I., Grigorescu PCs. Radiotherapy in the clinic. Medical publishing house, Bucharest, 1981. s-726. (similar).

3. Clark R.L, Ibanez M.L., Write E.C. // Arch. Surg. 1966. 92, 23.

4. Popovich V. Zyryanov BN. and other Intraoperative and electronic therapy of head and neck tumors. Tomsk. - Publishing house map Vector, 1999, 144 S. (similar).

5. Musabayev LI, Tyukalov SCI, Lisin, V.A. et al. Combined treatment of sarcomas of the soft tissues with the use of intraoperative lucev the th therapy and remote gamma-therapy // Medical radiology and radiation safety. Volume 42, 1997, No. 2. - p.58-63.

The method of combined treatment of locally common forms of differentiated thyroid cancer and its recurrence from postoperative course remote gamma-therapy (DHT) on the area of the postoperative scar and the area of regional lymph Gr 2 5 fractions per week, characterized in that on the bed of the removed tumor spend intraoperative radiation therapy (IORT) fast 6 MeV electrons with a single dose of 8 Gy, and after healing of wounds and the removal of the stitches hold DHT, the number of sessions which are calculated according to the formula

N=8,9(3,4-X-0,169), where N is the number of sessions postoperative DHT; X is the time interval in days between session IORT and DHT, provided that the dose of mixed irradiation (IORT and DHT) on the area of the removed tumor of the thyroid gland or cancer recurrence is for the treatment of 60 Gy in isaffected.



 

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