RU2744748C2 - Method for the treatment of squamous cell carcinoma of the head and neck - Google Patents

Abstract

FIELD: oncology.

SUBSTANCE: invention can be used to treat squamous cell carcinoma of the head and neck. Three-dimensional conformal radiation therapy (3DCRT) is performed. In this case, the planning of radiation therapy begins with the removal of the main dose fields, sequentially figuratively reproducing the target from different angles, with the subsequent targeted addition of smaller fields in the zones of deficiency of the dose of ionizing radiation, by analogy with segments in reverse planning (IMRT). Moreover, the first field is chosen at an angle of 160 ± 10 degrees so that it does not pass through the spinal cord. Next, the fields are built with a step of the gantry angle of 15-20 degrees counterclockwise: 160-140-120-100-80 ... 200 degrees. Moreover, the number of gantry angles can be from 12 to 35 fields, the fields can be duplicated "field-in-field".

EFFECT: method provides for 3D conformal irradiation at the IMRT and VMAT level on linear accelerators of any generation without the obligatory use of expensive planning systems due to the removal of the main dose fields with the subsequent targeted addition of smaller fields in the zones of deficiency of the ionizing radiation dose.

1 cl, 55 dwg, 2 ex

Description

The invention relates to medicine, namely to oncology, and can be used in the treatment of squamous cell carcinoma of the head and neck by exposure to ionizing radiation.

The proposed invention will make it possible to introduce modern technologies for radiation treatment of patients with head and neck tumors at the level of leading clinics in the world with the basic equipment of radiation therapy departments with equipment for planning and conducting standard 3D conformal radiation therapy. This corresponds to the current social demand and will significantly expand the coverage of the population with help in the form of modern precision radiation therapy.

Radiation therapy occupies one of the leading positions in the treatment of head and neck tumors. Long-term experience in the development of radiation therapy has demonstrated a steady increase in its role in oncological practice (Laskar S.G., 2006). The improvement of technical means, the introduction of methods for high-precision dose administration of ionizing radiation (IMRT, VMAT, IGRT, etc.), which can significantly reduce the volume of involuntarily irradiated healthy tissues and at the same time guarantee the delivery of the planned doses of ionizing radiation to the target, has become the main direction of development of modern radiation therapy. therapy (Christos A., 2008; Perez & Brady's, 2013).

The development of 3D radiation therapy planning systems laid the foundation for the evolution of radiation therapy. In general, thanks to three-dimensional planning, it was possible to significantly reduce the volume of irradiation of normal tissues, as well as, if necessary, to provide an escalation of the delivered doses of ionizing radiation, which significantly increased the effectiveness of treatment of patients with malignant formations of the head and neck. At the same time, precision irradiation methods using IMRT and VMAT have proven their obvious superiority over 2D and 3D conformal radiation treatment standards when used in patients with cancer of the oral cavity, pharynx, paranasal sinuses and other extracranial tumors of the head and neck closely adjacent to the cervical spinal cord. , brain, organs of vision, bone structures, salivary glands and other organs of risk.

Known standard methods of direct and reverse planning of radiation therapy for malignant tumors of the head and neck, described in a number of works, including S. H. Levitt et al. (eds.), Technical Basis of Radiation Therapy, Medical Radiology. Radiation Oncology, DOI: 10.1007 / 174_2011_322, Springer-Verlag Berlin Heidelberg 2012; Radiotherapy in Practice: External Beam Therapy. Edited by Peter Hoskin. Third Edition. Oxford University Press. 2019.

Standard methods of direct 3D planning provide a conformal distribution of the required dose of ionizing radiation in the irradiated volume with the maximum possible exclusion of radiation exposure to adjacent healthy tissues. Physical and mathematical calculations using this technique are carried out using the so-called direct planning. In this case, the configuration of the apparatus is changed manually (directly): the collimation system using a multi-leaf collimator, the dose rate, the intensity of the radiation beam. Due to these changes, the dose distribution is formed.

In recent years, modern methods of reverse planning have become firmly established in clinical practice, which make it possible to achieve a more homogeneous distribution of doses of ionizing radiation:

- IMRT (IMRT) - radiation therapy with modulation of the intensity (beam) of radiation. If the term "intensity" is here understood in accordance with GOST 15484-81 as the energy flux density, then it must be remembered that in the practice of radiation therapy, this modulation is performed by changing not the energy of the radiation beam, but the power of its fluence, that is, the number of particles per unit time ;

- VMAT - rotary (arc) irradiation with volume modulation of the intensity (radiation beam) - one of the options for IMRT.

The presented back-scheduling techniques for dose delivery allow to limit the radiation exposure to surrounding healthy organs (organs at risk) as much as possible while maintaining the optimal recommended target coverage indicators according to ICRU 83 (ICRU 83). A separate advantage of VMAT is a significant reduction in the time of irradiation sessions.

For head and neck tumors, when planning, the guideline is the following dose distribution parameters: Dose rationing - the focal dose is planned at 100% isodose. Not more than 0.03 cm ³ PTV should get> 110% of the prescribed dose. When a homogeneous target is irradiated, 95% of PTV should receive the prescribed dose (V100 ≥95%), while 99% of PTV should receive 93% of the prescribed dose (V93 ≥99%). When irradiated with a non-homogeneous target (for example, containing air), 95% of the PTV should receive at least 80% of the prescribed dose (V80 ≥95%). You should also take into account the proximity of the target to the skin surface, which negatively affects the distribution of doses. When contouring, it is possible to form indents from the skin surface of 4-6 mm. When determining the maximum allowable doses to critical organs, they use the QUANTEC criteria (Standards of Radiation Therapy. / Edited by A.D. Kaprin, A.A.Kostin, E.V. Khmelevsky. - M .: GEOTAR-Media, 2019) ...

In recent years, the use of the above technologies is strongly recommended within the framework of domestic and world clinical guidelines for the treatment of patients with head and neck tumors. At the same time, such technologies are still not publicly available due to their cost and complexity of implementation in practice.

The need for the active introduction of precision methods for administering doses of ionizing radiation is obvious, and ensuring their availability in routine practice is a priority in modern oncology. An alternative could be the adaptation of the less expensive and already widely implemented 3D conformal radiation therapy by developing new approaches to planning radiation treatment for patients with head and neck tumors.

The prototype is the method of irradiation of cancer patients mainly on cobalt remote sensing devices (RU 2290233 C2). The method makes it possible to form a dose field with the lowest possible dose drop across the target while reducing radiation exposure to normal tissues and skin. When preparing for irradiation of cancer patients on gamma-therapeutic devices based on cobalt for external radiation therapy, individual topographic and anatomical information about the patient is entered into the planning system. Further, taking into account the shape and size of the target, the location of critical organs and tissues, the main dose field is formed, after which the area of the dose deficit within the target is determined and the isocenters of additional dose fields are located in it. In this case, the width of the irradiation beams that form additional dose fields is 1.5-2.5 times less than the width of the main dose field, and the dose of the main field is 0.7-0.85 of the resulting dose within the target.

However, cobalt-based devices do not imply sufficient dose delivery accuracy to the target due to design features. The new generation of medical accelerators with a multi-lobe collimation system allows a wide range of delivery methods to be implemented, which can be used to achieve high positioning accuracy and delivery of the required dose to the target, while reducing radiation exposure to adjacent risk organs.

The technical result of the present invention is the development of a method of treatment with increased efficiency in the form of a greater degree of regression of the primary tumor, suppression of subclinical disseminated metastases due to the optimal regime of radiation exposure to the tumor with minimization of side effects of radiation.

The specified technical result is achieved due to the fact that, as in the known method, the dose distribution is formed by increasing the number of fields with smaller sizes by analogy with volume segmentation during reverse planning.

A feature of the proposed method is that the planning of radiation treatment begins with the removal of the main dose fields, sequentially figuratively reproducing the target from different angles, followed by the targeted addition of smaller fields in the zones of deficiency of the dose of ionizing radiation by analogy with the segments in reverse planning (IMRT), and the architecture planning is carried out as follows: the first field is chosen so that it does not pass through the spinal cord at an angle of 160 ± 10 degrees, then the fields are built with a step of the gantry angle of 15-20 degrees counterclockwise: 160-140-120-100-80 ... 200 degrees, and the number and choice of angles of gantry fields varies depending on the configuration of the irradiated target and can range from 12 fields to 35 fields, in addition, the fields can be duplicated "field-in-field".

The invention is illustrated by a detailed description, laboratory studies, a table, clinical examples and illustrations, which depict:

FIG. 1 - A field at a gantry angle of 165 degrees and an MLK configuration.

FIG. 2 - A field at a gantry angle of 122 degrees and with an MLK configuration.

FIG. 3 - Comparison of 3DCRT and VMAT plans: a) axial projection of CT topometry; b) transversal projection; c) coronal projection.

FIG. 4 - Comparison of dose-volume histograms of two plans (GDO): dotted line - VMAT, solid line - 3DCRT; contours: blue - salivary glands; pink - spinal cord; beige - lower jaw; blue - irradiated target.

FIG. 5 - A field with a multi-petal collimator configuration, which is open to a part of the lymph nodes on the left with a gantry rotation beginning 150 degrees with a step of 10 degrees, end-180: a) view from the beam; b) MLK configuration.

FIG. 6 - Field with a multi-petal collimator configuration, which is open to a part of the lymph nodes on the right with a gantry angle of 165 degrees: a) view from the beam; b) MLK configuration.

FIG. 7 - A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the left with a gantry rotation beginning: 150 degrees in 10 degree increments, end-120; a) view from the beam; b) MLK configuration.

FIG. 8 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a 120-degree gantry angle: a) view from the beam; b) MLK configuration.

FIG. 9 - Field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 100 degrees: a) view from the beam; b) MLK configuration.

Fig. 10 - Field with the configuration of a multi-petal collimator, which is open to the upper part of the oropharynx with a gantry angle of 100 degrees: a) view from the beam; b) MLK configuration.

Fig. 11 - A field with a multi-petal collimator configuration, which is open to a part of the lymph nodes on the right with a gantry rotation beginning 180 degrees with a step of 10 degrees, end-150: a) view from the beam; b) MLK configuration.

Fig. 12 - Field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 90 degrees: a) view from the beam; b) MLK configuration.

Fig. 13 - Field with the configuration of a multi-lobed collimator, which is open to the upper part of the lymph nodes with a gantry angle of 195 degrees: a) view from the beam; b) MLK configuration.

Fig. 14 - The field with the configuration of the multi-petal collimator, which is open to a part of the lymph nodes on the left with the rotation of the gantry beginning 210 degrees with a step of 10 degrees, end-240: a) view from the beam; b) MLK configuration.

Fig. 15 - Field with the configuration of a multi-petal collimator, which is open to a part of the oropharynx with a gantry angle of 240 degrees: a) view from the beam; b) MLK configuration.

Fig. 16 - Field with the configuration of a multi-petal collimator, which is open to a part of the oropharynx with a gantry angle of 255 degrees: a) view from the beam; b) MLK configuration.

Fig. 17 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 270 degrees: a) view from the beam; b) MLK configuration.

Fig. 18 - Field with the configuration of a multi-petal collimator, which is open to a part of the oropharynx with a gantry angle of 0 degrees: a) view from the beam; b) MLK configuration.

Fig. 19 - Field with the configuration of a multi-petal collimator, which is open to the upper part of the oropharynx with a gantry angle of 0 degrees: a) view from the beam; b) MLK configuration.

FIG. 20 - Field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 310 degrees: a) view from the beam; b) MLK configuration.

Fig. 21 - Field with a multi-petal collimator configuration, which is open to the lower part of the lymph nodes on the left with a gantry angle of 0 degrees: a) view from the beam; b) MLK configuration.

FIG. 22 - Field with a multi-petal collimator configuration, which is open to the lower part of the lymph nodes on the right with a gantry angle of 0 degrees: a) view from the bundle; b) MLK configuration.

Fig. 23 - A field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry rotation beginning 40 degrees with a step of 10 degrees, end-100: a) view from the beam; b) MLK configuration.

Fig. 24 - Field with the configuration of a multi-petal collimator, which is open to a part of the oropharynx with gantry rotation beginning 280 degrees with a step of 10 degrees, end-240: a) view from the beam; b) MLK configuration.

Fig. 25 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 0 degrees: a) view from the beam; b) MLK configuration: a) view from the beam; b) MLK configuration.

FIG. 26 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 260 degrees: a) view from the beam; b) MLK configuration.

FIG. 27 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 0 degrees: a) view from the beam; b) MLK configuration.

Fig. 28 - Field with the configuration of a multi-petal collimator, which is open to a part of the oropharynx with a gantry angle of 355 degrees: a) view from the beam; b) MLK configuration.

Fig. 29 - Field with the configuration of a multi-petal collimator, which is open to a part of the oropharynx with a gantry angle of 43 degrees: a) view from the beam; b) MLK configuration.

Fig. 30 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 138 degrees: a) view from the beam; b) MLK configuration.

Fig. 31 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 138 degrees: a) view from the beam; b) MLK configuration.

Fig. 32 - Comparison of the plans calculated by the method: a) upper - 3DCRT; b) bottom - VMAT.

FIG. 33 - Field with a multi-petal collimator configuration, which is open to the upper part of the lymph nodes on the left with a gantry angle of 165 degrees: a) view from the bundle b) MLK configuration.

FIG. 34 - Field with a multi-petal collimator configuration, which is open to the upper part of the lymph nodes on the right with a gantry angle of 165 degrees: a) view from the bundle b) MLK configuration.

FIG. 35 - Field with a multi-petal collimator configuration, which is open to the upper part of the lymph nodes on the left with a gantry angle of 145 degrees: a) view from the bundle b) MLK configuration.

FIG. 36 - Field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 115 degrees: a) view from the beam b) MLK configuration.

Fig. 37 - Field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 100 degrees: a) view from the beam b) MLK configuration.

FIG. 38 - Field with a multi-petal collimator configuration, which is open to part of the lymph nodes and oropharynx with a gantry angle of 90 degrees: a) view from the beam b) MLK configuration.

FIG. 39 - Field with a multileaf collimator configuration, which is open to part of the lymph nodes with a gantry angle of 75 degrees: a) view from the beam b) MLK configuration.

FIG. 40 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 65 degrees: a) view from the beam b) MLK configuration.

FIG. 41 - Field with a multileaf collimator configuration, which is open to a part of the lymph nodes with a gantry angle of 56 degrees: a) view from the beam b) MLK configuration.

FIG. 42 - Field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 50 degrees: a) view from the beam b) MLK configuration.

FIG. 43 - A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the right with a gantry angle of 0 degrees: a) view from the bundle b) MLK configuration.

FIG. 44 - Field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the left with a gantry angle of 195 degrees: a) view from the beam b) MLK configuration.

FIG. 45 - A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the right with a gantry angle of 185 degrees: a) view from the beam b) MLK configuration.

FIG. 46 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx and lymph nodes on the right with a gantry angle of 215 degrees: a) view from the beam b) MLK configuration.

FIG. 47 - Field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 255 degrees: a) view from the beam b) MLK configuration.

FIG. 48 - Field with a multi-petal collimator configuration, which is open to a part of the oropharynx and lymph nodes with a gantry angle of 260 degrees: a) view from the beam b) MLK configuration.

FIG. 49 - Field with a multi-petal collimator configuration, which is open to a part of the lymph nodes with a gantry angle of 280 degrees: a) view from the beam b) MLK configuration.

FIG. 50 - Field with a multileaf collimator configuration, which is open to part of the lymph nodes with a gantry angle of 285 degrees: a) view from the beam b) MLK configuration.

FIG. 51 - Field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 300 degrees: a) view from the beam b) MLK configuration.

FIG. 52 - Field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 307 degrees: a) view from the beam b) MLK configuration.

FIG. 53 - Field with a multi-petal collimator configuration, which is open to the lower part of the lymph nodes on the left with a gantry angle of 0 degrees: a) view from the bundle b) MLK configuration.

FIG. 54 - Field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 0 degrees: a) view from the beam b) MLK configuration.

FIG. 55 - Comparison of plans calculated by the method: a) upper plan -VMAT; b) lower plan - 3DCRT.

The method is carried out as follows.

Dosimetric planning is carried out. The field is selected as follows. The first field is chosen so that it does not pass through the spinal cord. The optimal angle is 160 ± 10 degrees. Next, the fields are built with a step of the gantry angle of 15-20 degrees in the range from 160-200 degrees counterclockwise, that is: 160-140-120-100-80 ... 200 degrees. The number and choice of angles of gantry fields varies depending on the configuration of the irradiated target and can range from 12 to 35 fields. In addition, the fields can be duplicated "field-in-field", while only the configuration of the MLK changes.

Figures 1 and 2 show examples with field configurations with different gantry angles and multi-leaf collimator. If we consider the option of the standard forward planning of a three-dimensional conformal plan (3DCRT), in which the configuration of the multi-leaf collimator is chosen in such a way as to completely repeat the shape of the irradiation target, then the load on the organs at risk is significantly higher than that of IMRT (VMAT) plans. At the same time, the homogeneity of the dose distribution within the target is also worse with standard 3D conformal radiation therapy.

Irradiation planning is based on the fact that the radiation exposure to the selected target is carried out using a large number of static asymmetric fields (segments), small in terms of the dose contribution and cross-sectional area, the summation of which provides an optimal dose distribution both inside the target and at the border with risk organs. As a result of applying this method of optimized forward planning, it is possible to obtain a dose distribution similar to the IMRT plan, but without modulating the radiation beam intensity.

Let's compare the calculated plans in the 3DCRT dosimetric planning system according to the proposed method and VMAT in different projections (Fig. 3). Topometric CT upper projection - 3DCRT plan, lower projection of topometric CT - VMAT plan. The normalization of the isodose distribution of the plans is the same. The minimum value of the isodose distribution is 50% of the prescribed dose. The maximum value is 110% of the prescribed dose.

The coverage of the dosimetric plan calculated by the VMAT method is more uniform over the target, however, in both plans it is within the recommended clinical guidelines (both plans are suitable for treating the patient) (Fig. 4). In this case, the radiation load on the organs at risk, for example, the salivary glands and the spinal cord, is even greater with VMAT planning than with direct planning, which favorably distinguishes three-dimensional conformal planning.

A detailed comparison of the plans obtained using our proposed three-dimensional conformal (3DCRT) and VMAT reverse planning, which is the gold standard for irradiation of head and neck tumors, confirmed the following:

- the target coverage of the proposed direct planning technique is somewhat inferior to the VMAT technique, but is within the recommended values for radiation treatment;

- in both plans, the necessary, according to the QUANTEC criteria, reduction of radiation exposure to risk organs was achieved.

Thus, both planning techniques can ultimately be considered equivalent and interchangeable. At the same time, unlike the dosimetry plans calculated by the VMAT method, the quality assurance for the plans calculated by the 3DCRT method is not a strictly regulated check, which also optimizes the resource costs for radiation treatment.

The method has been successfully applied at Moscow Scientific Research Institute for the Study of P.A. Herzen, which is confirmed by the following clinical observations.

Example 1.

Patient Y., 47 years old, was admitted with a diagnosis of Oropharyngeal cancer (tongue root) grade III, cT3N0M0. The patient considers herself ill since November 2015, when, under the supervision of an otolaryngologist at the place of residence, she received symptomatic therapy for chronic tonsillitis with a temporary positive effect. In the summer of 2016, aching pains appeared in the area of the root of the tongue, aggravated by swallowing. In November 2016, due to an increase in complaints, as well as the appearance of interference with swallowing, I independently turned to an oncologist at the place of residence. A malignant disease of the tongue root is suspected. I independently applied to P.A. Herzen, where the present diagnosis was established and morphologically confirmed. Histological examination from 15.12.2016 - biopsy from a tumor of the root of the tongue - particles of the mucous membrane with a cover of squamous epithelium, lymphoid base, areas of growth of undifferentiated cancer with high mitotic activity. To clarify the histogenesis of the neoplasm, an immunohistochemical study is necessary. IHC from 21.12.2016 with CD 45, CK 5/6, CD 20, CD 3, BCL2, BCL 6, CD 10, PAX 5, MUMI, CD 4, CD 8, Ki67, Cytokeratin (AE 1 / AE3): B tumor cells, the reaction with CK 5/6 is negative. They showed a positive reaction with cytokeratin. With other markers, the reaction in tumor cells is negative. There is a very large admixture of CD45 positive lymphoid cells. Among tumor cells, Ki 67 positive are determined in a very large number. Cytological study dated 05.12.2016. from a tumor of the oropharynx - a cytogram of squamous cell non-keratinizing cancer. Cytological examination of 12/14/2016 punctate l / u in / 3 of the neck on the right - cytogram of lymph node hyperplasia. Cytological examination of 01/17/2017 punctate l / u / 3 of the neck on the right - the cellular composition of the lymph node. IHC (p16 expression) dated 12/13/2016: an intense positive reaction was found in all tumor cells.

There is no asymmetry of the face and neck. Performs mimic tests satisfactorily. No trism. Speech is not broken. There is no language deviation. In the area of the root of the tongue on the right, a tumor of dense consistency, measuring 4.0 x 3.5 cm, with a partial transition beyond the midline and involvement of the left sections of the root of the tongue is palpable. The tumor spreads to the lateral wall of the oropharynx on the right in the region of the lower pole of the tonsil. In / 3 of the neck on the left and in the submandibular regions on both sides, single nodes of a densely elastic consistency up to 1.5 cm in diameter, mobile relative to the surrounding tissues, are determined. In the rest of the neck without focal pathology.

Endoscopy: The root of the tongue is elastic and mobile. Retrograde examination in the posterior 1/3 of the right ½ of the tongue root reveals an enhanced, convoluted submucosal vascular pattern against the background of a smooth, shiny mucosa. The epiglottis-pharyngeal fold is not changed. Left symmetrical sections without features. The epiglottis is of normal shape and size. The piriform sinuses are free on both sides. The larynx is preserved in all three sections, the mucous membrane is smooth, both ½ are mobile. The trachea was unremarkable. Conclusion: сr right 1/2 of the tongue root, endophytic form of growth.

MRI of the head and neck with intravenous contrast enhancement: The lingual right and right palatine tonsils are enlarged due to the area of the altered MR signal (hyperintense on T2 VI and STIR, hypointense - on T1 VI), spreading to the root of the tongue, measuring 30x28x45mm, deforming the lumen oropharynx. After the injection of a contrast agent, an intense and uneven accumulation of the latter is noted, mainly in the peripheral regions with a visualized hypointense central formation measuring 26x20x25 mm. Along the anterior and posterior edges of the sternocleidomastoid muscles, mainly on the right, there are enlarged lymph nodes ranging in size from 9mm to 42x12mm.

Ultrasound of the neck: In / 3 of the neck on the right (1/2), a lymph node with an uneven contour of a heterogeneous structure measuring 19.5x16x27mm is determined (puncture). In the middle / 3 and in / 3 of the neck, on both sides, lymph nodes with preserved structure without signs of atypia are determined with dimensions on the right up to 11x5mm, on the left up to 10x4mm.

A course of biological radiation therapy with the use of cetuximab according to the above scheme was carried out up to SOD 72 Gy on the area of primary tumor of the lymph nodes and up to SOD 54 Gy on the locoregional area of the oropharynx, including the pharyngeal lymph nodes and lymph collectors of the Ib-IV neck groups on both sides.

The treatment was carried out with a 7-day break in treatment at the peak of radiation reactions. At the end of the treatment, side effects were noted in the form of stage III epithelitis. CTC AE 4 versions of the severity of the mucous membranes of the oral cavity and pharynx, acne-like rash II stage. CTC AE 4 versions and stage II dermatitis. CTC AE 4 versions on the neck on both sides. Food by mouth in full. According to the assessment of the quality of life, the tolerability of the treatment was satisfactory.

The patient was discharged under observation at the place of residence.

At the follow-up examination after 2 months, there were no signs of relapse, regional and distant metastasis, as well as side effects of previous treatment, with the exception of xerostomia of the 1st stage. CTC AE 4 versions. Left under observation. Currently no signs of relapse for 39 months.

The use of the proposed method in the clinic makes it possible to achieve cure of the patient with minimal side effects, in contrast to the known schemes of chemoradiation therapy.

The calculation of the treatment plan was carried out according to the 3DCRT method in the XiO planning system. The plan consists of 27 fields, which included rotation fields:

1. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the left with a gantry rotation beginning 150 degrees (Fig. 5 a) with a step of 10 degrees, end-180 (Fig. 5 b).

2. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the right with a gantry angle of 165 degrees (Fig. 6 a, b).

3. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the left with a gantry rotation beginning 150 degrees in 10 degrees increments, end-120. (Fig. 7 a, b).

4. Field with a multi-blade collimator configuration that is open to a portion of the oropharynx with a 120-degree gantry angle. (Fig. 8 a, b).

5. Field with a multi-blade collimator configuration that opens to the top of the oropharynx with a 100 degree gantry angle. (Fig. 9 a, b).

6. Field with a multi-petal collimator configuration that opens onto the top of the oropharynx with a 100 degree gantry angle. (Fig. 10 a, b).

7. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the right with a gantry rotation beginning 180 degrees in 10 degrees increments, end-150. (Fig. 11 a, b).

8. Field with a multi-petal collimator configuration that opens onto the top of the oropharynx with a 90 degree gantry angle. (Fig. 12 a, b).

9. A field with a multileaf collimator configuration that is open to the top of the lymph nodes with a 195 degree gantry angle. (Fig. 13 a, b).

10. A field with a multi-petal collimator configuration, which is open to a part of the lymph nodes on the left with a gantry rotation beginning 210 degrees in 10 degrees increments, end-240. (Fig. 14 a, b).

11. Field with a multi-blade collimator configuration, which is open to a part of the oropharynx with a 240 degree gantry angle. (Fig. 15 a, b).

12. A field with a multi-blade collimator configuration that is open to a portion of the oropharynx with a gantry angle of 255 degrees. (Fig. 16 a, b).

13. Field with a multi-blade collimator configuration that is open to the oropharynx with a 270 degree gantry angle. (Fig. 17 a, b).

14. Field with a multileaf collimator configuration that is open to a portion of the oropharynx with a 0 degree gantry angle. (Fig. 18 a, b).

15. Field with a multi-petal collimator configuration that opens to the top of the oropharynx with a 0 degree gantry angle. (Fig. 19 a, b).

16. Field with a multi-petal collimator configuration that opens onto the top of the oropharynx with a 310-degree gantry angle. (Fig. 20 a, b).

17. Field with a multi-petal collimator configuration, which is open to the lower part of the lymph nodes on the left with a gantry angle of 0 degrees. (Fig. 21 a, b).

18. A field with a multi-petal collimator configuration, which is open to the lower part of the lymph nodes on the right with a gantry angle of 0 degrees. (Fig. 22 a, b).

19. Field with a multileaf collimator configuration, which is open to a part of the oropharynx with gantry rotation beginning 40 degrees in 10 degree increments, end -100. (Fig. 23 a, b).

20. Field with a multileaf collimator configuration, which is open to a part of the oropharynx with gantry rotation beginning 280 degrees in 10 degree increments, end-240. (Fig. 24 a, b).

21. A field with a multi-blade collimator configuration that is open to a portion of the oropharynx with a 0 degree gantry angle. (Fig. 25 a, b).

22. A field with a multileaf collimator configuration that is open to a part of the oropharynx with a gantry angle of 260 degrees. (Fig. 26 a, b).

23. A field with a multileaf collimator configuration that is open to a part of the oropharynx with a gantry angle of 0 degrees. (Fig. 27 a, b).

24. A field with a multi-blade collimator configuration, which is open to a part of the oropharynx with a gantry angle of 355 degrees. (Fig. 28 a, b).

25. Field with a multi-blade collimator configuration, which is open to a part of the oropharynx with a gantry angle of 43 degrees. (Fig. 29 a, b).

26. A field with a multi-blade collimator configuration, which is open to a part of the oropharynx with a gantry angle of 138 degrees. (Fig. 30 a, b).

27. Field with a multi-blade collimator configuration, which is open to a part of the oropharynx with a gantry angle of 138 degrees. (Fig. 31 a, b).

When comparing this plan with the plan calculated by the VMAT method, it can be seen that the isodose distributions of the plans are similar. (Fig. 32 a, b).

Example 2.

Patient G., 60 years old, was admitted with a diagnosis of Oropharyngeal cancer (right palatine tonsil), grade IV, cT2N2bM0. In anamnesis 36 years ago, lymphadenectomy was performed on the right neck for lymphadenitis. The patient considers herself ill since November 2016, when she noted sore throat when swallowing. Received no effect symptomatic therapy at the ENT doctor at the place of residence for exacerbation of tonsillitis. In January 2017, an additional examination revealed a neoplasm of the oropharynx and the patient was referred to an oncologist. I independently applied to P.A. Herzen, where the present diagnosis was established and morphologically confirmed. Histological examination from 03/15/2017: biopsy from the formation of the right palatine tonsil: particles of the mucous membrane with a cover of stratified squamous non-keratinizing epithelium, in one of the particles with a picture of squamous cell carcinoma in situ and foci of the beginning of invasive growth. Histological examination from 03/20/2017: biopsy from the formation of the submandibular region on the right: a fragment of fibrous tissue with lymphocytic infiltration and complexes of squamous cell non-keratinizing carcinoma. Cytological study of material from the formation of the submandibular region to the right of 03/07/2017 - a cytogram of squamous cell carcinoma with a tendency to keratinization. IHC (p16 expression) dated 03.24.2017: an intense positive reaction was found in all squamous cell carcinoma cells.

There is no face asymmetry. No trism. Performs mimic tests satisfactorily. Speech is not broken. In the right half of the oropharynx, along the posterior wall, a tumor is determined, of mixed growth, densely elastic on palpation, measuring 2.5x3 cm. In / 3 of the neck on the right, a postoperative scar without signs of inflammation is determined. There is a cicatricial deformity in the upper third of the neck on the right. On the right neck, single nodes are determined, up to 1.5 cm in size, dense on palpation, limitedly mobile. On the left neck without focal pathology.

Endoscopy: In the area of the right amygdala, a small-knobby infiltration of the right palatine tonsil of bright pink color is determined, bulging into the lumen of the oropharynx, up to 1.5 cm in size. The posterior palatine arch is not visually changed. Left symmetrical sections without features. The root of the tongue is symmetrical, anatomical, elastic, without signs of tumor infiltration. The epiglottis is of normal shape and size. All elements of the larynx are preserved, clearly visualized, the mucous membrane is smooth. Both larynxes are mobile, phonation. The lining department is free. Conclusion: sg of the oropharynx with lesions of the right palatine tonsil.

MRI with contrast enhancement: On the posterior wall of the oropharynx on the right, narrowing its lumen on the right and causing a mild deviation of the right palatine tonsil, a submucosal multicameral cystic formation of an irregularly rounded shape, with clear, even contours, with MR signs of a pseudocapsule, about 13x23x35mm in size, localized on the anterior surface of the long muscles of the neck and head at the level of the vertebral bodies C3, C2 and partially adjacent parts of the odontoid process of the C2 vertebra, without convincing MR signs of the proliferation of the formation in the projection of the sympathetic trunk. In the upper right parts of the neck along the lower medial contour, intimately adjacent to the right parotid salivary gland at the level of the vertebral body C3 and adjacent parts of the body C2, compressing the gland, a multicameral cystic-solid formation of an irregularly rounded shape is determined, with clear, even contours, with MR signs of a pseudocapsule, about 21x20x23mm in size. The right internal carotid artery and the right internal jugular vein are intimately adjacent to the medial contour of the formation in the projection of the course of the right hypoglossal, accessory and vagus nerves, without convincing MR signs of involvement of the above-described nerves in the process. The internal jugular vein is compressed by education. There were no enlarged lymph nodes and destruction of bone structures at the studied level. After the administration of a contrast agent (Magnevist 0.2 ml / kg body weight), there were no adverse reactions to the administration. Determined by its intensive and heterogeneous accumulation by the two above-described formations. No other areas of its pathological accumulation were found. Conclusion: MRI picture under a mucous multicameral cystic formation on the posterior wall of the oropharynx on the right without convincing MR signs of the spread of the formation (multicameral cyst?) In the projection of the sympathetic trunk, a picture of a multichamber cystic solid formation in the upper right parts of the neck along the lower medial contour right parotid salivary gland (altered lymph node ?, adenoma of the right parotid salivary gland?) without convincing MR signs of involvement of the right hypoglossal, accessory and vagus nerves in the process.

Ultrasound: At least three formations with reduced echogenicity up to 24x14x24mm are visualized in the right submandibular region in the area of the n / o scar. No focal pathology was found in the left submandibular region. In the structure of the posterior process of the right parotid salivary gland, a hyperplastic l / node up to 8x4x7 mm is visualized. In the neck area, hyperplastic l / nodes of the largest sizes are visualized: in the v / 3 on the right up to 10x4x12 mm, in the n / 3 on the left up to 12x3x5 mm.

A 5-day course of biological radiation therapy with the use of cetuximab according to the above scheme was carried out up to SOD 72 Gy on the area of the primary tumor and metastatic lymph nodes and up to SOD 54 Gy on the locoregional area of the oropharynx, including the retropharyngeal lymph nodes and lymph collectors of the neck of groups I-V on both sides. At the end of the treatment, resorption of the exophytic component of the tumor was noted.

The treatment was carried out with a 7-day break in treatment at the peak of radiation reactions. At the end of the treatment, side effects were noted in the form of stage II epitheliitis. CTC AE 4 versions of the severity of the pharyngeal mucosa, acne-like rash, stage I. CTC AE 4 versions and dermatitis I stage. CTC AE 4 versions on the neck on both sides). Food by mouth in full. According to the assessment of the quality of life, the tolerability of the treatment was satisfactory.

The patient was discharged under observation at the place of residence.

At the follow-up examination after 2 months, there were no signs of relapse, regional and distant metastasis, as well as side effects of previous treatment, with the exception of xerostomia of the 1st stage. CTC AE 4 versions. Left under observation. Currently no signs of relapse within 36 months.

The calculation of the treatment plan was carried out according to the 3DCRT method in the XiO planning system. The plan consists of 27 fields, which included rotation fields:

1. Field with the configuration of a multi-petal collimator, which is open to the upper part of the lymph nodes on the left with a gantry angle of 165 degrees (Fig. 33 a, b).

2. A field with a multileaf collimator configuration, which is open to the upper part of the lymph nodes on the right with a gantry angle of 165 degrees (Fig. 34 a, b).

3. A field with a multileaf collimator configuration, which is open to the upper part of the lymph nodes on the left with a gantry angle of 145 degrees (Fig. 35 a, b).

4. A field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 115 degrees (Fig. 36 a, b).

5. A field with a multi-petal collimator configuration, which is open to the upper part of the oropharynx with a gantry angle of 100 degrees (Fig. 37 a, b).

6. A field with a multi-petal collimator configuration, which is open to a part of the lymph nodes and oropharynx with a gantry angle of 90 degrees (Fig. 38 a, b).

7. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes with a gantry angle of 75 degrees (Fig. 39 a, b).

8. A field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 65 degrees (Fig. 40 a, b).

9. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes with a gantry angle of 56 degrees (Fig. 41 a, b).

10. A field with a multileaf collimator configuration, which is open to a part of the oropharynx with a gantry angle of 50 degrees (Fig. 42 a, b).

11. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the right with a gantry angle of 0 degrees (Fig. 43 a, b).

12. A field with the configuration of a multileaf collimator, which is open to a part of the lymph nodes on the left with a gantry angle of 195 degrees (Fig. 44 a, b).

13. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes on the right with a gantry angle of 185 degrees (Fig. 45 a, b).

14. A field with a multi-petal collimator configuration, which is open to a part of the oropharynx and lymph nodes on the right with a gantry angle of 215 degrees (Fig. 46 a, b).

15. A field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 255 degrees (Fig. 47 a, b).

16. A field with a multi-petal collimator configuration, which is open to a part of the oropharynx and lymph nodes with a gantry angle of 260 degrees (Fig. 48 a, b).

17. A field with a multileaf collimator configuration, which is open to a part of the lymph nodes with a gantry angle of 280 degrees (Fig. 49 a, b).

18. A field with a multi-petal collimator configuration, which is open to a part of the lymph nodes with a gantry angle of 285 degrees (Fig. 50 a, b).

19. A field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 300 degrees (Fig. 51 a, b).

20. A field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 307 degrees (Fig. 52 a, b).

21. A field with a multileaf collimator configuration, which is open to the lower part of the lymph nodes on the left with a gantry angle of 0 degrees (Fig. 53 a, b).

22. A field with a multi-petal collimator configuration, which is open to a part of the oropharynx with a gantry angle of 0 degrees (Fig. 54 a, b).

When comparing this plan with the plan calculated by the VMAT technique, it can be seen that the isodose distributions of the plans are similar (Fig. 55 a, b).

The developed method of direct 3D conformal planning of radiation treatment for patients with head and neck tumors is economically profitable and allows to significantly reduce the radiation exposure to the organs of risk, to carry out high-precision radiation treatment in medical institutions that were previously unavailable due to their insufficient technical equipment.

The inventive method of direct planning of radiation therapy is a full-fledged alternative to the currently considered optimal methods of reverse planning IMRT and VMAT. At the same time, radiation treatment can be carried out using less expensive old generation radiation therapy planning systems and linear accelerators, which is important for any generation. This is not only more profitable economically, but will also significantly expand the coverage of the population with help in the form of modern precision radiation therapy.

Claims (1)

A method of treating squamous cell carcinoma of the head and neck, which consists in conducting three-dimensional conformal radiation therapy (3DCRT), while the planning of radiation therapy begins with the removal of the main dose fields, sequentially figuratively reproducing the target from different angles, followed by the targeted addition of smaller fields in the zones the deficiency of the dose of ionizing radiation by analogy with the segments in reverse planning (IMRT), and the first field is chosen at an angle of 160 ± 10 degrees so that it does not pass through the spinal cord, then the fields are built with a step of the gantry angle of 15-20 degrees counterclockwise: 160-140-120-100-80 ... 200 degrees, and the number of gantry angles can be from 12 to 35 fields, the fields can be duplicated "field-in-field".

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