Malignant neoplasms of the orbit

CLINICAL PROTOCOL FOR DIAGNOSIS AND TREATMENT

Clinical Target Volume – clinical target volume

Gross Tumor Volume – clinically determined primary tumor

according to examination and radiography data organrisk – organs at risk Multileaf Collimator – multileaf collimator

GPP Good Clinical Practice

METHODS, APPROACHES AND DIAGNOSTIC PROCEDURES Diagnostic criteria: Early diagnosis of tumors of this localization is difficult due to asymptomatic course. The close connection between individual anatomical areas promotes rapid spread of the tumor through air-containing cavities and

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natural openings of the skull, which determines the specifics of their treatment [21,18,9, 10] (LE A).

The earliest and most frequent symptom of orbital sarcomas is initially transient, and then persistent edema of the upper eyelid. The first symptom may be diplopia, subsequently a feeling of heaviness appears, pain with movement of the eyeball, paresthesias in the face and head area. The pronounced stage of sarcoma is characterized by exophthalmos, displacement and limitation of eyeball mobility [8,9,10, 21] (LE A). Complaints: edema (swelling) of the upper eyelid; drooping of the upper eyelid (ptosis); appearance of a tumor formation in the orbit; impaired eyeball mobility, strabismus; redness of the eyeball; exophthalmos (proptosis, protrusion); eye pain, headaches; decreased vision up to blindness; impaired eyeball mobility, strabismus; bone defect of the temporal wall of the orbit; facial deformity. History:

Stage I-II – complaints of change in the palpebral fissure due to mild non-inflammatory edema of the upper eyelid (swelling), slight ptosis combined with chemosis. Smoothing of the upper orbito-palpebral fold. Due to tumor growth through the lacrimal gland capsule into adjacent tissues, extraocular muscle function is impaired early; patients develop strabismus, impaired eye movement to the sides. Compression of the eyeball by the tumor and elongation of its anteroposterior axis causes myopic astigmatism. Exophthalmos and eyeball displacement are still weakly expressed. On palpation under the upper and upper-outer edge of the orbit, an immobile dense formation with an irregular, bumpy surface can be determined.

CT shows – an additional tumor formation of irregular shape with indistinct and uneven contours in the lacrimal gland area; in stage two, destruction of a bone tissue area is possible.

Stage III – complaints of exophthalmos with displacement toward the nose or downward, reposition is difficult. On palpation in the upper-outer quadrant – a bumpy formation, not displaceable relative to underlying tissues. There is a tendency for perineural spread. Complaints of severe pain in the orbit due to compression of sensory nerves by the tumor. On CT – without contrast enhancement: isodense solid formation of homogeneous structure, contains no calcifications. Against the background of an enlarged orbit, adjacent bone structures show signs of destruction more often in the upper-outer, upper and outer walls of the orbit. On MRI T1-WI: solid formation of homogeneous structure, isointense MR signal. T2-WI: MR signal intensity is variable: more often isointense, hypointense tumors are usually hypercellular and

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belong to the basaloid subtype. Ultrasound semiotics: Echo structure of the lacrimal gland is heterogeneous, erosive changes in adjacent bone structures, iso- or hypoechoic formation.

Stage IV – complaints of more pronounced exophthalmos with displacement toward the nose, reposition is sharply difficult, almost absent. Complaints of headaches, ptosis, limitation of eyeball mobility. Patients complain of redness of the eyeball (red chemosis of the conjunctiva), visual acuity decreases, up to blindness due to optic nerve atrophy. CT or MRI shows – an additional tumor formation occupying the orbital cavity, extending to any of the following structures: frontal sinus, infratemporal fossa, cranial cavity. Metastases to regional lymph nodes, lungs, spine are possible. Laboratory parameters at various stages of the disease may be within normal limits. Physical examination: external examination of the face, symmetry and configuration of the face (facial asymmetry due to tumor deformity of soft tissues, organ, tumor growth and infiltration, impaired functional activity of the organ); exophthalmometry with determination of the degree of eyeball protrusion; palpation examination of the orbit, determination of impaired eyeball mobility to the sides; visometry – determination of visual acuity of both eyes; tonometry – determination of intraocular pressure; perimetry (as indicated) – determination of visual field defects palpation examination of lymph nodes of the submandibular area, neck on both sides (for presence or absence of regional metastases in lymph nodes). Laboratory studies: cytology – includes fine-needle aspiration biopsy (FNAB) of the orbital formation, lymph node, preparation of imprint smears from the tumor and cytological examination of the tumor to determine the morphological structure of the tumor; FNAB with cytological examination is possible when the tumor is localized in the anterior part of the orbit. NB! When the tumor is located at the orbital apex, aspiration is associated with the risk of eye damage [6,9,17] (LE A). If melanoma is suspected, FNAB is contraindicated due to the threat of dissemination of the orbital tumor [9,10,6, 17] (LE A). histology – includes biopsy of tumor tissue from the orbital tumor to determine the morphological structure of the tumor and its degree of malignancy (histological differentiation G). Instrumental studies: CT/MRI of the orbits, nasal cavity, paranasal sinuses, maxilla, ethmoid labyrinth cells – to determine the localization of the tumor process, its spread to adjacent organs and tissues; Ultrasound of the orbits – to determine the echo structure and degree of tumor vascularization;

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chest X-ray – to exclude distant metastases in the mediastinum or other concomitant diseases;

puncture biopsy of the orbital tumor, lymph node, preparation of smear-imprints from the tumor and cytological examination of the tumor to determine the morphological structure of the tumor;

biopsy of tumor tissue from the orbit, lymph node to determine the morphological structure of the tumor and its degree of malignancy (histological differentiation G);

intraoperative diagnostics includes – biopsy of tumor tissue, preparation of smear-imprints from the tumor and urgent histological examination of the removed tissue.

Indications for specialist consultations:

consultation with narrow specialists – as indicated.

On CT – sharply enlarged, edematous extraocular muscles, retrobulbar tissue edema, painful exophthalmos.

Clinically: painful proptosis without fever or elevated white blood cell count.

orbital diseases: inflammatory in nature, which can be localized in any part of the orbit. There are no cardinal symptoms distinguishing pseudotumor from malignant tumor.

In myositis – expansion of the muscle cone and its accumulation of contrast material.

Absence of signs of destruction of the bony walls of the orbit, which is usually observed in cancer.

The difference between malignant orbital tumor and pseudotumor is that in cancer exophthalmos is unilateral.

When the process is localized at the orbital apex – visual disturbances, optic neuropathy.

TREATMENT TACTICS AT THE OUTPATIENT LEVEL:

When detected, timely referral to an oncology dispensary to a specialized specialist, and treatment at the prehospital level is symptomatic.

3.1 Non-drug treatment:

Regimen III;

Diet – table No. 15.

Indicators of treatment effectiveness:

After organ-preserving treatment: Objective signs of absence of tumor, tumor regression, metastases. absence of exophthalmos; absence of deformities and strabismus; elimination of diplopia; restoration of the range of eyeball mobility; reduction of periorbital edema.

After orbital exenteration:

absence of residual tumor, ultrasound data on absence of metastases and recurrence;

CT, MRI data on absence of distant metastases;

satisfactory indicators of complete blood count, urinalysis, blood biochemical parameters;

adequate (without suppuration) healing of the postoperative orbital wound;

relatively satisfactory condition of the patient.

INDICATIONS FOR HOSPITALIZATION WITH INDICATION OF HOSPITALIZATION TYPE:

4.1 Indications for planned hospitalization:

presence in the patient of morphologically verified malignant orbital tumor, subject to specialized treatment with clinical group II;

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patients without morphological verification, but having clinical and diagnostic data of malignant orbital tumor, for conducting therapeutic-diagnostic surgery.

4.2 Indications for emergency hospitalization:

presence in the patient of morphologically verified malignant orbital tumor, subject to specialized treatment with bleeding or pain syndrome in clinical group II.

ORGANIZATIONAL ASPECTS OF PROTOCOL IMPLEMENTATION

7.1. List of protocol developers with indication of qualification data:

1) Adilbaev Galym Bazenovich – Doctor of Medical Sciences, Professor, "RSE on REM Kazakh Research Institute of Oncology and Radiology".

2) Kainazarova Maira Azimkhanovna – ophthalmologist of the head and neck tumor center, RSE on REM "Kazakh Research Institute of Oncology and Radiology".

3) Balmukhanova Aigul Vladimirovna – Doctor of Medical Sciences, Professor, ophthalmologist/oncologist, Corresponding Member of the NAS RK, Director of the Department of Clinical Work RSE on REM "Kazakh National Medical University named after S.D. Asfendiyarov".

4) Smagulova Kaldygul Kabakovna – Candidate of Medical Sciences, Head of the DSCT Department, chemotherapist, highest category physician, RSE on REM "Kazakh Research Institute of Oncology and Radiology".

5) Trushchenko Oleg Yurievich – RSE on REM "Kazakh Research Institute of Oncology and Radiology", radiologist of the head and neck tumor center.

6) Tabarov Adlet Berikbolovich – clinical pharmacologist, Head of the Innovation Management Department RSE on REM "Hospital of the Medical Center of the Administration of the President of the Republic of Kazakhstan".

List of references used:

1) Avetisov S.E., Kharlap S.I., Markosyan A.G. et al. Ultrasound spatial clinical analysis of the orbital part of the lacrimal gland in normal

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and in pathology//Collection of scientific papers of the international symposium "Diseases, tumors and traumatic lesions of the orbit". 2) Adilbaev G.B., Kim G.G., Kaibarov M.E., Mukhambetov M.M., Sadykov S.S. Role of neoadjuvant polychemotherapy and radiation therapy with radiomodification in complex treatment of maxillary sinus cancer//V Congress of Oncologists and Radiologists of the CIS, May 14-16, Tashkent 2008. P. 149; 3) Adilbaev G.B., Kim G.G., Mukhambetova G.A. Ways to improve the results of complex treatment of locally advanced maxillary sinus cancer//Bulletin of N.N. Blokhin RONC RAMS, 2009, vol. 20, No. 2 (suppl.1), p.54, Materials of the Eurasian Congress on Head and Neck Tumors, 2009, Minsk, Belarus 4) Aznabaev M.T., Gabdrakhmanova A.F. Clinical presentation and radiation diagnostics of lacrimal gland tumors//Problems of Ophthalmology. – 2004.– No. 1. – P.41 – 44. 5) Amiryan A.G. "Lacrimal gland tumors: features of clinical presentation at the onset of their growth", Collection of scientific papers of the international symposium "Diseases, tumors and traumatic lesions of the orbit" p. 55., Moscow 2005 6) Brovkina A.F., Zhiltsova M.G., Kaplina A.V. Fine-needle aspiration biopsy in the diagnosis of tumors of the visual organ: manual for physicians.- Moscow.2000.- p. 7) Brovkina A.F. Optic nerve meningioma//RMJ (clinical ophthalmology), 2001. - Volume 2. — No. 1. — P. 3—4. 8) Brovkina A.F. Diseases of the orbit//Eye diseases. Ed. by Kopaeva V.G. — M.: Medicine, 2002.- P. 411-449. 9) Brovkina A.F. Ophthalmic oncology: guide for physicians. — M.:Medicine, 2002. - 424 p. 9) Brovkina A.F. Diseases of the orbit. — 2nd edition. — M.: MIA, 2008. 256 p. ed. by prof. A.F. Brovkina. Tumors and tumor-like diseases of the visual organ: collection of scientific papers of scientific-practical conference, November 1-3/– Moscow, 2010. – 216 p. 10) Brovkina A.F. Radiation therapy in the treatment of tumors of the visual organ. Clinical Ophthalmology, 2003, vol.4, No.1, 15-19. 11) Vaganov A.A., Rostovtsev M.V., Ivanov K.A. Possibilities of computed and magnetic resonance tomography (CT and MRI) in the diagnosis of orbital neoplasms//Roentgenradiology of the XXI century, problems and hopes: abstracts of the VIII All-Russian Congress of Roentgenologists and Radiologists. — Chelyabinsk — Moscow, 2001.- P. 222. 12) Vazhenin A.V., Panova I.E. Selected issues of ophthalmic oncology. M.: RAMS, 2006. - 156 p. 13) Valsky V.V. On the possibility of differential diagnosis of optic nerve tumors according to CT data // Collection of scientific papers of the international symposium "Diseases, tumors and traumatic lesions of the orbit". - M., 2005. - P. 67 – 70. 14) Eastern European Sarcoma Study Group. www.eesg.ru 15) Zhiltsova M.G. Fine-needle aspiration biopsy in the diagnosis of tumors of the visual organ: Abstract of dissertation... candidate of medical sciences.– M., 2002.– 18 p.

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16) Zotova A.S. "Primary neoplasms of the orbit: structure and algorithms of clinical-radiological diagnostics" Abstract of dissertation, 2008 17) Malignant soft tissue tumors and skin melanoma: I.A. Gilyazutdinov, R.Sh. Khasanov, I.R. Safin, V.N. Moiseev — Moscow, Practical Medicine, 2010 - 204 p. 18) Kaynazarova M.A., Adilbaev G.B., Trushchenko O.Yu. "Features of clinical-diagnostic presentation of malignant lacrimal gland tumors. What should a practicing physician know?" Journal "Oncology of Kazakhstan", January 2017, pp. 176-179 19) Clinical recommendations "Diagnosis and treatment tactics for malignant orbital tumors", Staff of FSBI "Helmholtz Moscow Research Institute of Eye Diseases" of the Ministry of Health of the Russian Federation: Saakyan S.V., professor, MD, Honored Doctor of the Russian Federation, head of the department of ophthalmic oncology and radiology et al., September 24, 2015, Moscow. www.avo-portal.ru 22) Kropotov M.A. General principles of treatment of patients with primary head and neck cancer. N.N. Blokhin RONC RAMS, Moscow. Practical Oncology Vol.4, No.1 2003 20) Kulbakin D.E. Modern aspects of surgical treatment and rehabilitation of patients with cranio-orbito-facial tumors. Based on materials of the International 67th N.I. Pirogov Scientific Student Conference (Tomsk, 2008) edited by prof. Novitsky V.V. and MD Ogorodova L.M. 21) General guide to radiology: translated from English: in 2 volumes / ed. by Holger Pettersson, MD, - M.: RA "Spas", 1996. - Volume 1. - 668 p. 22) Oncology. Ed. by Chissov V.I., Daryalova S.L., M.I. Davydov - M.: GEOTAR-Media, 2008. - 1072 23) Paches A.P. Head and neck tumors. Clinical guide. Fifth edition. Moscow 2013, pp. 322-339; 24) Guide to chemotherapy of tumor diseases. Edited by N.I. Perevodchikova, V.A. Gorbunova. 4th edition, expanded and supplemented. Practical medicine. Moscow 2015; 25) Website of "Moscow Eye Clinic": http://mgkl.ru/patient/stati/ekzenteratsiyaglazni 26) Collection of scientific papers of the international symposium "Diseases, tumors and traumatic lesions of the orbit" Moscow, 2005. 27) Handbook of oncology. Edited by Jimmy Cassidy, Donald Bissett, Roy A.J. Spence, Miranda Payne. Translation from English by prof. V.A. Gorbunova. 2010 28) TNM Atlas K. Wittekind, F.L. Greene, R.V.P. Hutter, M. Klimpfinger, L.H. Sobin, 2007. 29) Trufanov G.E., Burlachenko E.P. Radiation diagnostics of eye and orbital diseases. St. Petersburg, "Elbi-SPb", 2009 30) Trukhacheva N.G. Ophthalmosonography in complex diagnostics of orbital tumors. Abstract of dissertation, candidate of medical sciences.– Tomsk, 2008 31) Cherekaev V.A., Reshetov I.V., Davydov D.V. et al. / Clinical presentation and topographic anatomy of cranio-orbito-facial tumors // Russian Oncological Journal. – 2007. – No.2. pp.14-20

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Translation of "symptoms" field

32) Shugol O.M. Neoplasms of the cranio-orbital-facial region (neuro-ophthalmological symptomatology, surgical treatment): Abstract of dissertation for candidate of medical sciences. - Chelyabinsk, 2006. - 24 p. 33) American Joint Committee on Cancer (AJCC). AJCC Cancer Staging Manual, 7th ed. Edge S.B., Byrd D.R., Carducci M.A. et al., eds. New York: Springer; 2009; 34) Blay J.Y. Trabectedin's contribution to the treatment of sarcomas. Expert Rev Anticancer Ther. 2013: 13 (6, Suppl 1): s3-9. doi: 10.1586/era.13.48. 35) http://GlazKakAlmaz.ru/wp_content/uploads/2015/01/Sleznaya_zheleza_1.jpg http://yaviju. Com/stroenie-glaza/sleznaya-zheleza-glavnyi- uvlazhnitel-glaza.htm. 36) http://www.med-ed.virginia.edu/courses/rad/radbiol/index.htm 37) TDF Plan: Biological Models. http://www.eyephysics.com/tdf/models.htm 38) http://ozradonc.wikidot.com/radiobiology:contents 39) *International Union Against Cancer (UICC). TNM Classification of Malignant Tumours, 7th ed. Sobin L.H., Gospodarowicz M.K., Wittekind Ch., eds. New York: Wiley-Blackwell; 2009. 40) Members of the Sarcoma Disease Site Group «Adjuvant Chemotherapy Following Complete Resection of Soft Tissue Sarcoma in Adults» Evidence-based Series 11-2 Version 2 – EDUCATION AND INFORMATION 2014, Canada 41) https://www.cancercare.on.ca/common/pages/UserFile.aspx?fileId=34382 42) Murphy B.A Carcinoma of the head and neck. In: Handbook of cancer chemotherapy. Skeel R.Т., Khleif S.N. (eds). 8 th Edition. Lippincott Williams & Wilkins.2011: 69-63; 43) NCCN Clinical Practice Guidelines in Oncology: head and neck. Available at Accessed March 2011; 44) NCCN Clinical Practice Guidelines in Oncology, Version 1.2015, 45) NCCN, Clinical Practice Guidelines in Oncology: head and neck ver. 1, 2017 46) Pignon J.-P., le Maitre A., Maillard A. et al. Meta-analysis of chemotherapy in head and neck cancer (MACH-NC): an update on 93 randomised trials and 17,346 patients. Radiother Oncol. 2009; 92:4-14. 47) Practical essentials of IMRT, second edition, K.S. Clifford Chao (USA) Lippincott Williams&Wilkins 48) Perez and Brady`s Principles and Practice of Radiation Oncology, 5th edition 49) Target Volume Delineation for Conformal and Intensity-Modulated Radiation Therapy» Radiation Oncology. L.W. Brady, S.E. Combs, J.J. Lu 50) Trigo J, Hitt R, Koralewski P, et al. Cetuximab monotherapy is active in patients (pts) with platinum-refractory recurrent/metastatic squamous cell carcinoma of the head and neck (SCCHN): Results of a phase II study (abstract). ASCO Annual Meeting Proceedings (post-meeting edition). J Clin Oncol 2004; 22:5502 51) Posner M.R., Hershor D.M., Blajman C.R. et al. Cisplatin and fluorouracil alone or with docetaxel in head and neck cancer. N Engl J Med. 2007; 357 (17): 1705-1715 52) Blanchard P., Bourhis J., Lacas B. et al. Taxan-Fluorouracil as induction chemotherapy in locally advanced head and neck cancers: an individual patient data metaanalysis of the meta-analysis of chemotherapy in head and neck cancer group. J Clin Oncol. 2013; 31(23): 2854-2860;

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Approved by the Joint Commission on Quality of Medical Services of the Ministry of Health of the Republic of Kazakhstan dated November 10, 2017

Protocol No. 32

MALIGNANT NEOPLASMS OF THE ORBIT

Introductory Part

Protocol Code(s) ICD-10:

ICD-10

Code Name

C 69.5

Malignant neoplasm of lacrimal gland and duct

C 69.6

Malignant neoplasm of orbit

C 69.8

Lesions of eye and adnexal apparatus extending beyond one or more of the above-mentioned localizations

Date of protocol development/revision: 2017.

Abbreviations used in the protocol:

IV

IM

ALT

AST

APTT

HIV

IOP

IJV

HSC

Gy

ONH

HGD

GIT

MN

ON

PONH

ELISA

CT

RT

intravenous

intramuscular

alanine aminotransferase

aspartate aminotransferase

activated partial thromboplastin time

human immunodeficiency virus

intraocular pressure

internal jugular vein

highly specialized medical care

gray

optic nerve head

high-grade dysplasia

gastrointestinal tract

malignant neoplasm

optic nerve

papilledema

enzyme-linked immunosorbent assay

computed tomography

radiation therapy

MRI

MDT

INR

IJV

ROD

PNS

PTI

PET

TFD

CVS

SFD

MRND

ChT

HNTC

ECG

ECHO

Rh

SFMC

FFP

TNM 2D RTC 3D CRT

PTV

CTV

GTV OR

MLC

IORT

IMRT IGRT ECLIPSE

DICOM CBCT Aria

magnetic resonance imaging

multidisciplinary team

international normalized ratio

internal jugular vein

regional oncology dispensary

paranasal sinuses

prothrombin index

positron emission tomography

total focal dose

cardiovascular system

single focal dose

modified radical neck dissection

chemotherapy

head and neck tumor center

electrocardiography

echocardiography cardiac ultrasound

blood Rh factor

soluble fibrin-monomer complexes

fresh frozen plasma

Tumor Nodulus Metastasis - international classification of stages of malignant neoplasms

2D Radiotherapy Conventional - 2-dimensional conventional (ordinary, standard) radiation therapy

3D Conformal Radiotherapy - 3-dimensional conformal RT

Planning Target Volume – planning target volume

Intraoperative Radiotherapy – intraoperative radiation therapy

Intensity Modulated Radiotherapy – intensity-modulated radiation therapy

Image Guided Radiotherapy – image-guided radiation therapy

Eclipse dosimetric planning system

Digital Imaging and Communications in Medicine - industry standard for creating, storing, transmitting and visualizing medical images and documents of examined patients

Cone Beam Computed Tomography - cone beam computed tomography Aria information management system

Protocol users: oncologists, ophthalmologists, maxillofacial surgeons, otolaryngologists, general surgeons, general practitioners.

Patient category: adults.

Evidence level scale:

A High-quality meta-analysis, systematic review of RCTs or large RCT with very low probability (++) of systematic error results. B High-quality (++) systematic review of cohort or case-control studies or high-quality (++) cohort or case-control studies with very low risk of systematic error or RCT with not high (+) risk of systematic error. C Cohort or case-control study or controlled study without randomization with low risk of systematic error (+). D Case series description or uncontrolled study, or expert opinion.

Classification:

Currently, a clinical classification by TNM has been developed only for lacrimal gland carcinoma and orbital sarcoma [37] (LOE A).

Clinical classification of lacrimal gland carcinoma.

Clinical TNM classification

T – primary tumor

Tx – assessment of primary tumor not possible

T0 – primary tumor not detected

T1 – tumor up to 2.5 cm in size, confined within the lacrimal gland.

T2 – tumor 2.5-5 cm in size, confined within the lacrimal gland

T3 – tumor with periosteal involvement

T3a – tumor up to 5 cm in size with involvement of the periosteum of the lacrimal fossa

T3b – tumor larger than 5 cm with periosteal involvement

T4 – tumor with extension to orbital soft tissues, optic nerve or eyeball with or without bone involvement, tumor extending beyond the orbit with involvement of adjacent tissues and organs, including the brain.

In each case, histological confirmation of lacrimal gland carcinoma diagnosis and identification of histological tumor type is required.

Clinical classification of orbital sarcoma

The classification presented below applies only to soft tissue and bone sarcomas of the orbit.

In each case, histological confirmation of diagnosis and identification of histological tumor type is required.

Clinical TNM Classification:

T - primary tumor

Tx - assessment of primary tumor not possible

T0 - primary tumor not detected

T1 - tumor up to 15 mm in size

T2 - tumor more than 15 mm in size

T3 - tumor of any size with involvement of orbital walls and/or other orbital tissues

T4 - tumor with involvement of the eyeball or adjacent structures - eyelids, temporal fossa, nasal cavity, paranasal sinuses and/or brain

N1 - regional metastases present

Regional lymph nodes

The regional lymph nodes for the orbit are the parotid lymph nodes, submandibular, cervical lymph nodes located along the neurovascular bundle of the neck.

N - regional lymph nodes

Nx - insufficient data to assess the status of regional lymph nodes

N0 - no signs of metastatic involvement of regional lymph nodes

N1 - metastases in a single lymph node on the affected side up to 3 cm or less in greatest dimension

N2 - metastases in one or more lymph nodes on the affected side up to 6 cm in greatest dimension or metastases in lymph nodes of the neck on both sides, or on the opposite side up to 6 cm in greatest dimension

N2a - metastases in a single lymph node on the affected side up to 6 cm in greatest dimension

N2b - metastases in multiple lymph nodes on the affected side up to 6 cm in greatest dimension

N2c - metastases in lymph nodes on both sides or on the opposite side up to 6 cm in greatest dimension

N3 - metastasis in a lymph node more than 6 cm in greatest dimension

M - distant metastases

MX - insufficient data to determine distant metastases

M0 - no signs of distant metastases

M1 - distant metastases present

Pathomorphological classification

pT - criteria for pT category correspond to those for T category.

Stage grouping for orbital tumors - currently not developed.

In practice, general characteristics of stages of malignant tumors adopted in international practice are applied:

Stage 0 - "carcinoma in situ" (cancer in place). This is a small tumor that does not invade adjacent tissues. It is in equilibrium, at each moment in time an equal number of tumor cells die and form again;

Stage I, II, III - the higher the stage number, the larger the size of the primary tumor, its spread to regional lymph nodes and adjacent organs;

Stage IV - characterized by the presence of distant metastases.

Differential diagnosis and justification for additional investigations [9,13,38,39] (LE A):

Diagnosis | Justification for differential diagnosis | Investigations for exclusion of diagnosis | Criteria Tumor-like Pseudotumor - formation

Differential diagnosis is conducted based on morphological findings. | displacement of the eyeball to the opposite side from the site of lesion. Pseudotumor can sometimes be bilateral.

Wegener's granulomatosis | The most severe pathology of autoimmune nature. Begins gradually, proceeds in three stages. In the first - localized involvement of the upper respiratory tract, middle ear and visual organ is detected. Then internal organs are affected, persistent fever, weight loss. The third stage is terminal with signs of cardiopulmonary and renal failure. Prognosis for both vision and life is severe. Characterized by a triad: necrotizing granulomas of the upper and lower respiratory tract, glomerulonephritis and necrotizing vasculitis. | CT, MRI of orbits, puncture biopsy of orbit with morphological examination of punctate. CT of chest, ultrasound of kidneys. Differential diagnosis is conducted based on morphological findings. | On radiographic examination, carcinoma of the mucous membrane presents with a defect of the cortical plate. The bone edges of the crater-like defect are usually not sharp, lacunar in shape. The bone edges of the crater-like defect are usually not sharp. Carcinoma does not cause reactive changes in the bone. In orbital carcinoma, the triad of symptoms characteristic of Wegener's disease is absent. Characteristic triad of symptoms: skin involvement in the form of plaques and nodules, mediastinal adenopathy and rarefaction of bones of distal phalanges of fingers.

Sarcoidosis | Systemic granulomatous disease, nature unknown. Possible selective involvement of the orbit. Sarcoid granulomas spreading at the orbital apex are difficult to diagnose. | Differential diagnosis is conducted based on morphological findings. |

Dermoid cyst of orbit | Appears in children under 5 years of age, however only 40% of them seek help after age 18. Grows extremely slowly. Located in the area of bone sutures, more often in the upper-inner quadrant of the orbit. More often does not form exophthalmos. Painless swelling of the upper eyelid corresponding to the location of the cyst. However, one variety - ball-shaped dermoid cyst of the orbit can cause exophthalmos with displacement. | On CT, not only the altered bone walls are visualized, but also the cyst itself with capsule. Differential diagnosis is conducted based on morphological findings. | Imaging diagnosis: most typical feature: the parenchyma of the formation is partially or completely represented by adipose tissue. A mass with clear contours, localized in the upper part of the orbit, more often in the area of the frontozygomatic suture, does not accumulate contrast. Thinning and deepening of the bone edge of the orbit in the zone of cyst location. In ball-shaped cyst, the orbit is enlarged, in the lateral wall behind the zygomatic process - an oval bone defect.

Pleomorphic adenoma of lacrimal gland | The most common benign tumor of the lacrimal gland. 2% of all neoplasms. Slowly progressive. | CT, MRI of orbits, puncture biopsy of orbit with morphological examination of punctate. | In malignant tumor of the lacrimal gland - invasive tumor localized in the upper-lateral quadrant of the orbit outside the muscle cone.

painless proptosis. Displacement of the eyeball downward and medially.

9 Lymphoproliferative diseases: lymphoid hyperplasia, non-Hodgkin lymphoma.

orbit. 50% of all lacrimal gland neoplasms. More than 95% of all benign orbital neoplasms.

These include both benign and malignant formations.

Lymphoid hyperplasia (10-40%): reactive hyperplasia, benign polyclonal, atypical hyperplasia.

The most common orbital lymphoma is lymphoma arising from mucosa-associated lymphoid tissue

(MALT);

diffuse large B-cell lymphoma, typically a systemic lymphoproliferative process;

others: Burkitt lymphoma, T- cell lymphoma. Localized in the anterior extraconal compartment punctate.

Imaging diagnostics: typical

sign – a mass lesion of the lacrimal gland, accompanied by its diffuse enlargement with remodeling of adjacent bony structures.

Localization: anterosuperior extraconal segment of the orbit, in most cases the tumor forms in the orbital lobe of the lacrimal gland.

is based on morphological examination CT, MRI of orbits, ultrasound of lymph nodes of regional zones. Biochemical blood analysis: LDH, alkaline phosphatase.

Cytological examination of punctate is not informative, histological examination with

IHC is necessary.

Differential diagnosis is based on morphological conclusion

Ultrasound – semiotics: A-scan – internal structure regular, echogenicity from medium to high. B-scan – formation with smooth contours, surrounded by pseudocapsule, inelastic, may contain cystic inclusions. CT semiotics: Excavation of bony structures forming the lacrimal fossa (2/3 of cases). Punctate calcifications within the tumor (1/3 of cases)

Most typical manifestation: asymptomatic mass in the anterior part of the orbit. In 50% of cases downward displacement of the eyeball is noted. When the conjunctiva is involved, the tumor is visualized on ophthalmoscopic examination.

Skin involvement is atypical (its presence is characteristic of T-cell lymphomas and leukemias). About 50% of lymphoproliferative diseases of the orbit progress to systemic non-Hodgkin lymphoma. Often associated with NHL of other localization.

10 Cavernous hemangioma of the orbit

Optic nerve meningioma orbit; the center of the formation projects into the superolateral quadrant, with creeping spread to other parts of the orbit. The lacrimal gland is often involved in the process. In 25% of cases both orbits are affected in high histological grade tumors.

Diffuse infiltrative growth patterns occur with spread to intraconal muscles or optic nerves.

A mass lesion of the orbit, consisting of dilated vessels, intensely enhancing with contrast material. In 80% of cases localized intraconally.

Bounded by a pseudocapsule, consisting of compressed adjacent structures

Benign, slowly growing tumor arising from arachnoid cells of the sheath of the intraorbital portion of the optic nerve. Of all

On ultrasound – hyperechoic heterogeneous retrobulbar mass. On Doppler in its structure areas of decreased blood flow and low resistance are detected. On contrast MRI – early heterogeneous contrast enhancement in central portions, which over time becomes homogeneous. Differential

diagnosis is based

on morphological conclusion On CT slices, the presence of linear or punctate calcifications is typical.

is based on Symptoms: painless proptosis, diplopia, visual deterioration, increased IOP. On fundoscopy – retinal striae. Age of patients from 10 years. Grows slowly, progressively increasing in size, unlike capillary hemangiomas, which are prone to spontaneous regression. In some cases compresses orbital structures and leads to bone remodeling. During pregnancy grows faster.

Typical manifestation: unilateral loss of vision, proptosis. More common in middle-aged and elderly women.

Radiological "tramtrack sign" reflects 11 Subperiosteal orbital abscess orbital meningiomas, 10% are primary, 90% are secondary and arise from structures adjacent to the orbit (cranio-orbital).

Shape: tubular (65%)>on a stalk (25%)>fusiform (10%). Forms around the nerve.

Less commonly eccentric or has a stalk Collection of pus between the lamina papyracea and the orbital periosteum, usually at the medial wall of the orbit. Source of inflammation: sinusitis of the ethmoid labyrinth cells and maxillary sinus.

Less commonly – bacterial septicemia, skin infection, penetrating injury. Sinusitis causes periostitis of the orbital walls, orbital phlegmon and cellulitis develop. Then a subperiosteal

abscess forms. This is a rare complication

of sinusitis morphological conclusion

Orbital CT.

CBC,

bacterial culture of conjunctival discharge or from the wound surface. Administration

of IV antibiotics and

external drainage of the abscess help in establishing the correct diagnosis.

contrast enhancement along the sides of the hypodense optic nerve. Typical sign – accumulation of cerebrospinal fluid under the sheath of the distal part of the optic nerve – perioptic cyst.

Typical manifestation: painful exophthalmos, sinusitis, upper respiratory tract infection, fever. Edema of periorbital soft tissue with erythema, decreased vision.

On contrast-enhanced CT slices appears as a hypodense lentiform fluid collection, sometimes with gas, with peripheral contrast enhancement, which is located along the medial orbital wall, accompanied by lateral displacement of the medial rectus muscle.

12

Medication Treatment:

List of essential medicines: No.

INN of drug Method of administration LE p/p antimicrobial agent for prevention of postoperative inflammation of the anterior segment of the eye

Tobramycin 0.3%,

2 drops 6 times a day, 10 C [6] eye drops days synthetic glucocorticosteroid with anti-inflammatory, antiallergic, desensitizing effects, agent for prevention of postoperative inflammation of the eye and orbit

dexamethasone 0.4%, eye drops, eye ointment 2 drops 2-3 times a day, C [6]

0.1%,

days. Ointment under lower

eyelid 1-2 times a day.

antibacterial agent for prevention of postoperative inflammation of the eye and orbit

cefazolin 500 mg, 1000 mg

IM, once a day, 7 days

C [6]

antimicrobial agent for prevention of postoperative inflammation of the eye and orbit

metronidazole 500 mg

IV, once a day, 5 days anti-inflammatory agent for prevention of postoperative inflammation of the anterior segment of the eye

diclofenac sodium 0.1% /5.0 ml

2 drops 3 times a day, 15 C [6] days With systemic use provides anti-inflammatory, antiallergic, desensitizing, anti-shock, antitoxic and immunosuppressive effects

methylprednisolone 125 mg, 500 mg

IV once a day, 3 days

D–C [6]

Surgical intervention: none.

TREATMENT TACTICS AT INPATIENT LEVEL: Treatment goals: clarification of diagnosis; elimination of tumor focus and metastases; achievement of complete or partial regression, stabilization of tumor process. Multidisciplinary approach: Initial assessment and development of treatment plan for the patient requires a multidisciplinary team (MDT) of physicians with experience in treating this group of patients. Also, implementation and prevention of consequences of radical surgery, RT and CT should be carried out by specialists knowledgeable about these diseases – namely head and neck tumor surgeon-oncologist, ophthalmic oncologist, radiologist and chemotherapist.

Management tactics:

Histological form TNM stage Treatment tactics squamous cell carcinoma

T1-T2,N0

Surgery-orbitotomy, adenocarcinoma +PCT(4-6 courses) lacrimal gland cancer infantile embryonal T3-4,N0,any Surgery (tumor carcinoma.

T stage,N + removal, exenteration) malignant fibrous

+PCT+RT

histiocytoma.

NB! According to NCCN Conference Materials, USA, 2006.

Treatment of malignant orbital tumors depending on stage:

Stages I–II (T1–2 N0).

Combined treatment: Surgical intervention via various approaches with postoperative external beam radiation therapy at total dose 60-70 Gy to the focus. For poorly differentiated tumors – irradiation of regional metastasis zone on the tumor side at total dose 66-70 Gy, neoadjuvant courses of polychemotherapy with

subsequent surgical treatment, anti-recurrence courses of

polychemotherapy in the postoperative period [32,59,46,49,47,26,67] (LE A);

Stage III (T1–2 N1 M0).

Combined treatment: surgery via external approach + external beam radiation therapy at total dose 60–70 Gy to the postoperative bed of primary tumor. Regional metastasis zones on the tumor side are irradiated at total dose 50 Gy. In case of insufficient effectiveness of radiation treatment – radical neck

dissection. In the postoperative period anti-recurrence adjuvant courses of polychemotherapy [32,59,46,49,47,26,67] (LE A); Stages III–IV A (T3–4 N0–3 M0). Option I: Complex treatment – surgical intervention via various approaches with postoperative external beam radiation therapy at total dose 70 Gy to the main focus and adjuvant courses of chemotherapy [32,59,46,49,47,26,67] (LE – A); Option II: In presence of contraindications to surgery and patient refusal of surgery neoadjuvant courses of polychemotherapy, external beam radiation therapy at total dose 60–70 Gy to the focus and 66-70 Gy to the regional lymph node zone on the affected side (N0) [2,32,59] (LE A); Option III: Neoadjuvant polychemotherapy and radiation therapy to the main focus total dose 50-70 Gy. [3,22,33] (LE B); Option IV: Preoperative radiation therapy with radiomodifying properties + surgery via various approaches, postoperative courses of polychemotherapy [33] (LE A), [3] (LE B); Stage IVB Palliative radiation therapy or chemotherapy in oncology dispensary conditions [33,59] (LE A). Treatment of clinically determined regional metastases:

Surgical intervention in presence of regional metastases is determined by the degree of tumor spread at initial staging. These recommendations apply to performing neck dissection as part of surgery on the primary tumor. In general, patients undergoing removal of primary tumor will undergo neck dissection on the affected side, as these lymph nodes have the highest risk of tumor involvement.

Type of neck dissection (radical, modified or selective) is determined according to preoperative clinical staging and surgeon's discretion. It is based on initial preoperative staging N1 – selective or modified radical neck dissection; N2 - selective or modified radical neck dissection; N3 – modified or radical neck dissection. Treatment of recurrent metastatic cancers:

Operable primary cancers must be radically removed again if technically feasible, and salvage surgery must be performed for recurrence of regional metastases after treatment. For regional metastases with no previous treatment, formal neck dissection or modified dissection should be performed depending on clinical situation. Non-surgical treatment is also clinically justified [32,59] (LE A).

Non-medication treatment: Patient regimen during conservative treatment – general. In early postoperative period – bed rest or semi-bed rest (depending on surgery volume and concomitant pathology). In postoperative period – ward.

Diet – Table No. 15, after surgical treatment Table No. 1, with concomitant diabetes mellitus pathology Table No. 9.

Radiation and chemotherapeutic treatment depends on factors related to tumor characteristics and the patient's general condition. The main goals of therapy are cure of the tumor, preservation or restoration of organ functions, and reduction of treatment complications. Successful treatment outcomes typically require a multidisciplinary approach. Chemotherapeutic and radiation treatment must be well-organized and supervised by chemotherapists and radiologists who have knowledge of treatment specifics and complications in this patient population.

The goal of radiation therapy is post-radiation regression of residual tumor (radical radiation program) or prevention of recurrence.

Radiation therapy techniques for malignant orbital tumors:

2-dimensional conventional (standard) radiation therapy (2DRTC);

3-dimensional conformal radiation therapy (3DCRT);

intensity-modulated radiation therapy (IMRT);

image-guided radiation therapy (IGRT);

intraoperative radiation therapy (IORT) (this technology is not currently applied).

Currently, the standard of radiation therapy is becoming 2D-RTC - 2-dimensional conventional (ordinary, standard) radiation therapy, 3D CRT - conformal radiation therapy, IMRT - intensity-modulated radiation therapy, IGRT - image-guided radiation therapy, which requires the use of 3D radiation planning and application of linear accelerators with multileaf collimators. RT is used as an independent treatment modality and in combination with other methods, most often with surgical. Currently, no significant differences have been identified in local control, distant metastasis, and overall survival between preoperative and postoperative RT groups.

RT therapy can be prescribed by a radiologist only after determination of cytological or histological, and often immunohistochemical, tumor type.

visual diagnostic methods (CT, MRI);

exacerbation and decompensation of severe concomitant pathology of the cardiovascular, respiratory, and other systems;

uncontrolled psychomotor agitation, inadequate patient behavior acute myocardial infarction, acute intracranial hemorrhage (stroke) within the last 9 months;

severe general condition of the patient, Karnovsky performance status below [score], consciousness on Glasgow scale below 12 points.

therapy.

In lacrimal gland cancer, RT in the postoperative period allows reduction of recurrence rates. Total dose not less than 65 Gy with conventional fractionation [10,50,60] (LE A).

The method of combined organ-preserving treatment of malignant orbital tumors using orbitotomy with maximum tumor excision, radiation therapy, and chemotherapy is accepted as the closest analogue of the proposed invention. It has a number of advantages over ablative exenteration. It allows enhancement of the therapeutic component. In case of residual tumor cells in the orbit, radiation therapy causes their death. At the same time, it has some disadvantages. First, external beam gamma therapy entails a number of serious early and late complications. Early complications include post-radiation keratitis, keratopathy, dermatitis, iridocyclitis, neuroretinopathy.

Late complications of post-radiation therapy include developing hypoplasia or asymmetry of facial tissues, sometimes requiring reconstructive surgery, dental deformities, deterioration of visual functions due to developed cataracts and corneal changes, optic nerve atrophy. Second, radiation therapy in some cases leads to development of secondary tumors (sarcomas, carcinomas, leukemia). Third, some histogenetic tumor types may exhibit resistance to radiation destruction mechanisms.

5.3 Medication treatment:

Chemotherapy is medicinal treatment of malignant cancerous tumors aimed at destroying or slowing the growth of cancer cells using special drugs, cytostatics.

Cancer treatment with chemotherapy occurs systematically according to a specific regimen, which is selected individually. As a rule, chemotherapy regimens for tumors consist of several courses of taking certain drug combinations with pauses between courses for restoration of damaged body tissues.

There are several types of chemotherapy that differ by purpose of prescription: neoadjuvant chemotherapy for tumors is prescribed before surgery, with the goal of reducing an inoperable tumor to enable surgery, as well as to identify cancer cell sensitivity to drugs for further prescription after surgery; adjuvant chemotherapy is prescribed after surgical treatment to prevent metastasis and reduce risk of recurrence; therapeutic chemotherapy is prescribed to reduce metastatic cancerous tumors.

Depending on the location and type of tumor, chemotherapy is prescribed according to different regimens and has its own characteristics.

Indications for chemotherapy: cytologically or histologically verified malignant orbital tumors in treatment of unresectable tumors; metastases in regional lymph nodes; tumor recurrence; satisfactory blood picture in the patient: normal hemoglobin and hematocrit levels, absolute granulocyte count – more than 200, platelets – more than 100,000; preserved liver, kidney, respiratory system, and cardiovascular system function; possibility of converting inoperable tumor process to operable;

patient refusal of surgery; improvement of long-term treatment outcomes in unfavorable histological tumor types (poorly differentiated, undifferentiated) [33] (LE A). Contraindications to chemotherapy: Contraindications to chemotherapy can be divided into two groups: absolute; relative. Absolute contraindications: hyperthermia >38 degrees; disease in decompensation stage (cardiovascular system, respiratory system, liver, kidneys); presence of acute infectious diseases; mental illnesses; ineffectiveness of this type of treatment, confirmed by one or more specialists; tumor disintegration (threat of bleeding); severe patient condition according to Karnofsky scale 50% and less. Relative contraindications: pregnancy; body intoxication; active pulmonary tuberculosis; persistent pathological changes in blood composition (anemia, leukopenia, thrombocytopenia); cachexia.

Below are the regimens of the most frequently used polychemotherapy modes for morphologically verified malignant orbital tumor. They can be used for both neoadjuvant (induction) chemotherapy and adjuvant polychemotherapy, with subsequent surgical intervention or radiation therapy, as well as for recurrent or metastatic tumors.

Indications and choice of antitumor drug therapy regimen depend on the histological form of the tumor: adenoid cystic carcinoma (accounts for more than 60%), malignant fibrous histiocytoma, chemodectoma (paraganglioma), malignant tumors of the skin and conjunctiva (squamous cell carcinoma) and sarcomas (account for 11 to 26% of all malignant orbital tumors). Depending on the tissue origin of sarcomas, leiomyosarcoma, angiosarcoma, neurosarcoma, liposarcoma, osteosarcoma, chondrosarcoma are distinguished.

The main combinations currently recognized for squamous cell carcinoma are cisplatin with 5-fluorouracil (PF) and docetaxel with cisplatin and 5-fluorouracil (TPF). This combination of chemotherapy drugs has become the "gold standard" when comparing the effectiveness of various chemotherapy drugs in the treatment of squamous cell carcinoma for all major multicenter studies [33,61] (LE A).

Among targeted drugs, cetuximab has currently entered clinical practice [33, 61] (LE A).

23

The most active antitumor agents for squamous cell carcinoma are considered for both 1st and 2nd lines: platinum derivatives (cisplatin, carboplatin), fluoropyrimidine derivatives (5-fluorouracil), anthracyclines, taxanes – paclitaxel, docetaxel. Effective drugs for adenoid cystic carcinoma and squamous cell carcinoma also include doxorubicin, capecitabine, bleomycin, vincristine, cyclophosphamide.

When conducting neoadjuvant, adjuvant, or independent polychemotherapy for squamous cell carcinoma, the following regimens and combinations of chemotherapy drugs may be used: PF: cisplatin 75-100 mg/m2 IV, day 1; 5-fluorouracil 1000 mg/m2 24-hour IV infusion (96-hour continuous infusion) days 1-4; course repetition every 21 days. CpF: carboplatin (AUC 5.0-6.0) IV, day 1; 5-fluorouracil 1000 mg/m2 24-hour IV infusion (96-hour continuous infusion) days 1-4; course repetition every 21 days. PCap: cisplatin 75 mg/m2 IV day 1; capecitabine 1000 mg/m2 orally twice daily, days 1-14; course repetition every 21 days. PP: paclitaxel 175 mg/m2, IV, day 1; cisplatin 75 mg/m2, IV, day 2; course repetition every 21 days. PC: paclitaxel 175 mg/m2, IV, day 1;

carboplatin (AUC 6.0), IV, day 1; course repetition every 21 days. TP: docetaxel 75 mg/m2, IV, day 1; cisplatin – 75 mg/m2, IV, day 1; course repetition every 21 days. TPF: docetaxel 75 mg/m2, IV, day 1; cisplatin 75-100 mg/m2, IV, day 1; 5-fluorouracil 1000 mg/m2, 24-hour intravenous infusion (96-hour continuous infusion), days 1-4; course repetition every 21 days. PPF: paclitaxel 175 mg/m2, IV, day 1, 3-hour infusion; cisplatin 75 mg/m2, IV, day 2; 5-fluorouracil 500 mg/m2, 24-hour intravenous infusion (120-hour continuous infusion), days 1-5; course repetition every 21 days.

24

cetuximab 400 mg/m2, IV (infusion over 2 hours), day 1 of cycle 1, cetuximab 250 mg/m2, IV (infusion over 1 hour), days 8, 15 and days 1, 8 and 15 of subsequent cycles; cisplatin 75-100 mg/m2, IV, day 1; 5-fluorouracil 1000 mg/m2, 24-hour intravenous infusion (96-hour continuous infusion) days 1-4; repeat cycles every 21 days depending on hematological recovery. CAP(a): cisplatin 100 mg/m2, IV, day 1; cyclophosphamide 400-500 mg/m2, IV day 1; doxorubicin 40-50 mg/m2, IV, day 1; repeat cycles every 21 days. PBF: 5-fluorouracil 1000 mg/m2, IV days 1,2,3,4; bleomycin 15 mg, days 1,2,3;

cisplatin 120 mg day 4; repeat cycle every 21 days. MPF: methotrexate 20 mg/m2, days 2 and 8; fluorouracil 375 mg/m2, days 2 and 3; cisplatin 100 mg/m2, day 4; repeat cycle every 21 days NB! when resectability of the primary tumor or recurrent tumor is achieved, surgical treatment may be performed no earlier than 3 weeks after the last administration of chemotherapy drugs. Targeted therapy: The main indications for targeted therapy are: locally advanced squamous cell carcinoma of the head and neck in combination with radiation therapy; recurrent or metastatic squamous cell carcinoma of the head and neck in case of ineffectiveness of previous chemotherapy; monotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck when previous chemotherapy is ineffective;

Cetuximab is administered once a week at a dose of 400 mg/m2 (first infusion) as a 120-minute infusion, then at a dose of 250 mg/m2 as a 60-minute infusion. When using Cetuximab in combination with radiation therapy, treatment with cetuximab is recommended to begin 7 days before the start of radiation treatment and continue weekly administration of the drug until the end of radiation therapy [33,46,61,62] (LE A).

In patients with recurrent or metastatic squamous cell carcinoma of the head and neck in combination with platinum-based chemotherapy (up to 6 cycles), cetuximab is used as maintenance therapy until signs of disease progression appear. Chemotherapy begins no earlier than 1 hour after the end of cetuximab infusion.

25

In case of skin reactions to cetuximab administration, therapy can be resumed using the drug in reduced doses (200 mg/m2 after the second reaction and 150 mg/m2 – after the third.

Monotherapy chemotherapy is recommended:

in debilitated elderly patients;

with low hematopoietic parameters;

with pronounced toxic effect after previous courses

of chemotherapy;

in conducting palliative courses of chemotherapy;

in the presence of comorbid pathology with high risk of complications.

Monochemotherapy regimens:

Repeat cycle every 21 days.

Repeat every 21 days.

methotrexate 40 mg/m2, IV, or IM day 1;

Repeat cycle every week.

capecitabine 1500 mg/m2, orally daily days 1-14;

vinorelbine 30 mg/m2, IV day 1;

cetuximab 400 mg/m2, IV (infusion over 2 hours), first administration, then

cetuximab 250 mg/m2, IV (infusion over 1 hour) weekly;

methotrexate, vinorelbine, capecitabine in monotherapy are most often used as second line.

For osteosarcoma, chondrosarcoma mesenchymal dedifferentiated, malignant fibrous histiocytoma, the following regimens and combinations of chemotherapy drugs are possible [16,19,33,43,46,61]

(LE A):

HD MTX:

high-dose methotrexate 12 g/m2, IV with calcium folinate once every 2 weeks, for 8 weeks.

AI:

ifosfamide 2 g/m2, days 1-5 IV;

doxorubicin 75 mg/m2, 72-hour infusion, IV.

IE:

ifosfamide 1800 mg/m2, days 1-5 IV;

etoposide 100 mg/m2, days 1-5.

GemTax: gemcitabine 675 mg/m2, IV, 90-minute infusion on days 1 and 8;

docetaxel 75 mg/m2, day 8.

MAID:

mesna OD 8000 mg/m2, as a 96-hour infusion (2000 mg/m2, per day for 4 days) doxorubicin 60 mg/m2, as a 72-hour infusion, IV 26

ifosfamide 6000 mg/m2, as a 72-hour infusion or 2000 mg/m2 IV as a 4-hour infusion, days 1-3. dacarbazine 900 mg/m2, as a 72-hour infusion, dissolved together with doxorubicin. Interval 3-4 weeks. ADIC: doxorubicin 90 mg/m2, as a 96-hour infusion, IV; dacarbazine 900 mg/m2, as a 96-hour infusion, dissolved together with doxorubicin. Interval 3-4 weeks CyADIC: cyclophosphamide 600 mg/m2, IV on day 1 doxorubicin 60 mg/m2, as a 96-hour infusion IV dacarbazine 1000 mg/m2, as a 96-hour infusion, dissolved together with doxorubicin. Interval 3-4 weeks Monochemotherapy: doxorubicin 60-75 mg/m2, IV once every 3 weeks [33,43,16,57,61] (LE A); doxorubicin 30 mg/m2, days 1-3; ifosfamide 5 mg/m2 IV or IV infusion on day 1 or 1.6-2.5 g/m2/day for 5 days with Mesna calculated as 20% + 100% of the ifosfamide dose simultaneously with it; gemcitabine 1200 mg/m2, over at least 120 minutes on days 1 and 8 every 21 days with a fixed infusion rate of 9-10 mg/m2/min;

pazopanib 800 mg, once daily orally, long-term (until progression). For patients with soft tissue sarcomas (except liposarcomas and GIST) with progression within 12 months after starting neoadjuvant or adjuvant therapy. Depending on individual tolerability, the daily dose of the drug may be decreased or increased in 200 mg increments, with the maximum daily dose not exceeding 800 mg. trabectedin 1.3 mg/m2, as a 24-hour infusion.

List of essential medicines: Medicines Dose, frequency, route of administration

LE

Alkylating agents – platinum complex compounds Cisplatin 75-100 mg/m2, solution, IV A carboplatin AUC 5-6, IV A Alkylating agents – chloroethylamines cyclophosphamide

mg/m2, IV

A Alkylating agents – triazines Dacarbazine

mg/m2, as a 72-96 hour infusion, IV

A Pyrimidine antagonists - fluoropyrimidines

fluorouracil

mg/m2, 24-hour IV infusion (96-hour A continuous infusion) days 1-4, IV Microtubule inhibitors – taxanes docetaxel

mg/m2, solution, IV

A paclitaxel

A 27 Antimetabolites – folic acid antagonists methotrexate 20-40 mg/m2, IV, IM A Pyrimidine antagonists – fluoropyrimidines capecitabine

mg/m2, days 1-14, tablets, oral

A Microtubule inhibitors – vinca alkaloids vinorelbine A Monoclonal antibodies to growth factors and their receptors cetuximab

mg/m2, first administration, then cetuximab 250 mg/m2, A

weekly, IV Antitumor antibiotics – anthracyclines.

mg/m2, as a 96-hour infusion, IV

A Antitumor antibiotics – bleomycins.

mg days 1,2,3, IV, IM

A Alkylating agents – chloroethylamines Ifosfamide

mg/m2, as a 72-hour infusion, IV

A Acrolein antidote Mesna A Antimetabolites – cytidine analogues Gemcitabine

mg/m2, days 1 and 8, IV

A Small molecule protein kinase inhibitors Pazopanib

mg, once daily long-term, tablets, oral

A Microtubule inhibitors - alkaloid Trabectedin 1.3 mg/m2, as a 24-hour infusion, IV B List of additional medications: Dose, frequency, route of administration

Medications

Antiemetic therapy

ondansetron

24-16 mg 30 minutes before chemotherapy, day 1 A

aprepitant 125 mg orally 1 hour before CT on day 1, 80 mg A (morning) days 2 and 3 dexamethasone 12 mg orally 30 min before CT on day 1, 8 mg A (morning) orally on day 2, day 3 and day 4

Antibacterial therapy

cefazolin 1.0 g, 1.0 g, 3 times daily, 7 days, IM B ceftazidime 1.0 g, 1.0 g, 3 times daily, 7 days, IM B ceftriaxone 1.0 g, 1.0 g, 2 times daily, 7 days, IM B cefuroxime sodium 1.0 g, 1.0 g, 2 times daily, 7 days, IM B cefepime 1.0 g, 1.0 g, 2 times daily, 7 days, IM B imipenem + cilastatin

mg, 2 times daily, 5-7 days, IM

A amikacin

mg, calculated as 10 mg/kg, 2 times daily, 7 days, IM

B ciprofloxacin

mg, 100 mg, 2 times daily, 5-7 days, IV

B ofloxacin 0.2 g, 0.2 g, 2 times daily, 7 days, IV B metronidazole

ml, 100 ml, 2 times daily, 5 days, vials, IV B

Antifungal therapy

fluconazole

mg, 100 mg IV, once, vials, IM

B Plasma substitutes hydroxyethyl starch

once daily up to 3 days, IV

A dextran

ml, 400 ml, 2 times daily 2-3 days, IV

Parenteral nutrition. Rehydration therapy

amino acid complex for

ml, 500 ml, once daily, 5-7 days, IV

A 28 parenteral nutrition dextrose 5% - 400 ml, 400 ml IV 2 times daily, 5-7 days, IV A sodium chloride 0.9% - 400 ml, 400 ml IV 2-3 times daily, 5-7 days, A IV Analgesics ketoprofen 1 ml, 1 ml, IM 2-3 times daily 5-7 days, IV B diclofenac sodium

– 3 times daily, 7-10 days, IM

B tramadol hydrochloride

ml, 1 ml 2-3 times daily, IM

Hormonal therapy

mg, 30-60-90 mg, once daily, days 1-5, IV A

mg, 4-8-12-16-20 mg, once daily days 1-5 A

human insulin

IU, 4-6 IU once daily, 2-10 days

A Antispasmodics (NB! use after registration in the territory of RK) platyphylline hydrotartrate 1.0 ml, 1 ml 1-3 times daily, 1-7 days, IM, IV B Bronchodilators aminophylline

ml, 6-10 mg/kg/day, 3 times daily, 10 days, IM

A theophylline 0.2 g, 0.2 g, 2-4 times daily, 10-15 days, tablets B oral Anticoagulants nadroparin calcium 0.3 ml, 0.3 ml once daily, SC B enoxaparin sodium 0.2 ml, 0.2 ml once daily, SC B heparin

thousand IU, 5000-10000 IU, once daily, IV or SC A

Antiemetic agent metoclopramide

mg, 10-20 mg, 1-2-3 times daily, days 1-5, IM, A

Mucolytic therapy

ambroxol

ml, 2 ml, 3 times daily, 7-10 days, IM

Sedative therapy

neostigmine methylsulfate 1.0 ml, 1 ml, 1-2 times daily, 1-10 days, IM B

Antipyretic therapy

acetylsalicylic acid 0.5 g, 0.5 g, 2 times daily, tablets, oral A paracetamol 0.5 g, 0.5 g, 3 times daily, tablets, oral A

Hemostatic therapy

aminocaproic acid 5% -100 ml, 100 ml, once daily, days 1-5, IV A etamsylate 12.5% - 2 ml, 2 ml, 2 times daily, days 1-5, IM A

Diuretic therapy

furosemide 1% 2 ml, 2 ml 1-3 times daily, days 1-5, IM A spironolactone

mg, 100 mg, once daily, 5-14 days, oral

Antianemic therapy

iron (III) hydroxide 100-200 mg IM, IV 3-5 times per week, IM, IV A polyisomaltose iron (III) hydroxide dextran 100-200 mg IM, IV 3-5 times per week, IM, IV A Epoetins epoetin-alfa 40000 IU/1 ml once weekly, SC A epoetin-beta

IU/kg once weekly, SC

A darbepoetin alfa

mcg once every 21 days, SC

Hematopoietic therapy

filgrastim 0.5 million IU (5 mcg) per 1 kg SC once daily or 5 mcg/kg from A day 5-7, SC, IV lenograstim

mcg (5 mcg/kg) once daily, until achieving A

stable neutrophil level SC, IV 29 pegfilgrastim*

mg once every 21 days, SC

A Granulocyte-macrophage colony-stimulating factor molgramostim* 5-10 mcg/kg daily, 7-10 days, SC A

Antihistamine therapy

diphenhydramine

ml – 10 mg, 10 mg, 1-2 times daily, IM

A chloropyramine

mg, 25 mg, 3-4 times daily, tablets, oral

neostigmine methylsulfate 1.0 ml, 1 ml, 1-2 times daily, 1-10 days, IM B Ointment and oil preparations chloramphenicol+methyluracil

g, 20-40 mg per day

B Antiseptic preparations hydroxymethylquinoxalinedioxide 10 mg/ml for external use, 20 ml per day povidone iodine

ml, 30 ml per day

brilliant green 1%-10 ml, 2-3 ml per day, externally ethanol 70%, 3-5 ml per day, externally octenidine dihydrochloride

ml, 20-30 ml per day, externally

hydrogen peroxide 3%-40 ml, 5-1 ml per day, externally

Chemoradiotherapy: When conducting simultaneous chemoradiotherapy, the following chemotherapy regimens are recommended [69,70,71,72,73] (LE A): cisplatin 20-40 mg/m2, IV weekly, during radiation therapy;

radiation therapy at a total focal dose of 66-70 Gy. Single focal dose - 2 Gy x 5 fractions per week;

carboplatin (AUC 1.5-2.0) IV, weekly, during radiation therapy;

radiation therapy at a total focal dose of 66-70 Gy. Single focal dose 2 Gy x 5 fractions per week; cetuximab 400 mg/m2, IV infusion (infusion over 2 hours), one week before the start of radiation therapy, then cetuximab 250 mg/m2, IV (infusion over 1 hour) weekly during radiation therapy. Treatment of unresectable tumors: Concurrent chemotherapy or radiation therapy: cisplatin 100 mg/m2 intravenous infusion at a rate not exceeding 1 mg/min with pre- and post-hydration on days 1, 22, and 43 during radiation therapy to the tumor bed at a total focal dose of 70 Gy (single focal dose 2 Gy) and the area of regional lymph nodes on the affected side at a total focal dose of 44-64 Gy (up to 70 Gy for large metastases) [48,10] (LE A);

external beam radiation therapy to the primary tumor site at a total focal dose of 70 Gy and regional lymph nodes at a total focal dose of 44-64 Gy (up to 70 Gy for large metastases). For low-grade tumors (N0), regional lymph nodes are not irradiated; If after completion of treatment the tumor becomes resectable, radical surgical intervention is possible [48,10] (LE A).

Surgical treatment is divided into organ-preserving (various types of orbitotomy with removal of orbital tumor) and ablative (orbital exenteration). Types of surgical interventions [7,8,9,10] (LE A): transcutaneous orbitotomy (superior, medial, inferior) with removal of orbital tumor; transconjunctival orbitotomy with removal of orbital tumor; subperiosteal orbitotomy with removal of orbital tumor; lateral or osteoplastic orbitotomy with removal of orbital tumor; removal of orbital tumor via Killian approach, via Smith approach; removal of orbital tumor via transcranial approach orbital exenteration with preservation (or without) of eyelids; supraperiosteal, subperiosteal orbital exenteration extended orbital exenteration with removal of nasal cavity tumor (with nasal amputation and reconstruction of postoperative defect); extended maxillectomy with orbital exenteration; various types of neck lymph node dissection; removal of facial bone tumors with defect reconstruction (high-tech medical care). Indications for surgical treatment: cytologically or histologically verified malignant neoplasms of the orbit; in the absence of verification due to difficulty performing fine-needle aspiration biopsy of the orbit, therapeutic-diagnostic surgery is performed – orbitotomy with express histological examination of surgical material; in the absence of contraindications to surgical treatment;

All surgical interventions for malignant tumors are performed under general anesthesia. Contraindications to surgical treatment for malignant neoplasms of the orbit: presence of signs of inoperability and severe concomitant pathology in the patient; undifferentiated orbital tumors, for which radiation treatment or chemotherapy may be offered as an alternative; synchronously existing and advanced inoperable tumor process of another location, for example lung cancer, etc.; chronic decompensated and/or acute functional disorders of the respiratory, cardiovascular, urinary systems, gastrointestinal tract; allergy to drugs used in general anesthesia; signs of extensive hematogenous metastasis, disseminated tumor process. Signs of tumor inoperability: tumor involvement of the following structures is associated with poor prognosis or classified as stage T4b (for example, inoperability associated with technical impossibility of obtaining a clear margin);

31

significant involvement of orbital bone structures, spread of tumor process to the nasopharynx, pterygopalatine fossa, infratemporal fossa, to the dura mater and brain involvement; direct spread through the optic nerve canal, superior orbital fissure, to the chiasm, internal carotid artery; direct spread of metastases to mediastinal structures, prevertebral fascia, or cervical vertebrae.

Further management: Follow-up schedule: first six months – monthly; second six months – every 1.5–2 months; second year – every 3–4 months; third–fifth years – every 4–6 months; after five years – every 6–12 months; Evaluation of treatment effectiveness is conducted based on the following examination methods: external examination; visometry; slit-lamp biomicroscopy; ophthalmoscopy; exophthalmometry; ultrasound of tumor bed; neck ultrasound; chest X-ray; CT, MRI of orbits, brain, nasal cavity, paranasal sinuses; abdominal ultrasound. repeat cytological or histological examination of accessible areas of recurrent tumor. Treatment of disease recurrence.

Local recurrences are treated surgically and with combined therapy. For unresectable recurrences and distant metastases, palliative chemotherapy or radiation therapy is performed. Regional lymphogenous metastases are treated surgically (radical cervical lymph node dissection) [32,59] (LE A).

In the presence of residual tumor, radical surgical intervention is performed followed by postoperative radiation therapy at a total dose of 70 Gy (single dose 2 Gy) to the area of the primary tumor focus (preferred option). Radiation therapy or concurrent chemotherapy is also possible. If residual tumor is not detected during clinical and instrumental examination, radiation therapy is performed on the tumor bed according to a radical program. As a treatment option, repeat surgical intervention with subsequent postoperative radiation therapy is possible [32] (LE A).

Palliative care for patients with malignant orbital tumors:

• for severe pain syndrome, treatment is carried out in accordance with the recommendations of the protocol "Palliative care for patients with chronic progressive diseases in the incurable stage, accompanied by chronic pain syndrome";
• in the presence of bleeding, treatment is carried out in accordance with the recommendations of the protocol "Palliative care for patients with chronic progressive diseases in the incurable stage, accompanied by bleeding".

Preventive measures:

Early initiation of treatment, its continuity, comprehensive nature, consideration of patient individuality, return of the patient to active work.

Primary prevention:

• combating tobacco smoking and alcohol;
• rationalization of nutrition;
• increasing physical activity and combating excess weight;
• reducing exposure to carcinogenic chemical and physical factors (production, natural environment, housing);
• prevention of exposure to infectious carcinogenic factors.

Secondary prevention:

• monitoring of risk groups;
• detection and treatment of precancerous diseases, inflammatory processes.

Tertiary prevention:

Use of medications that allow restoration of the immune system after antitumor treatment (antioxidants, multivitamin complexes), adequate nutritional regimen rich in vitamins and proteins, cessation of harmful habits (smoking, alcohol consumption), prevention of viral infections and concomitant diseases, regular preventive examinations by an oncologist, regular diagnostic procedures (chest radiography, ultrasound of liver, kidneys, cervical lymph nodes).

Indicators of treatment effectiveness and safety of diagnostic and treatment methods described in the protocol:

• "tumor response" – tumor regression after treatment; - relapse-free survival (three- and five-year); - patient "quality of life" according to the ECOG-WHO scale and Karnofsky scale

The effect of treatment is evaluated according to WHO criteria:

• complete response – disappearance of all lesion foci for a period of at least 4 weeks;
• partial response – greater than or equal to 50% reduction of all or individual tumors in the absence of progression of other foci;
• stabilization – (no change) reduction of less than 50% or increase of less than 25% in the absence of new lesion foci;
• progression – increase in size of one or more tumors by more than 25% or appearance of new lesion foci.

Final expected outcome – preservation of life

Treatment duration – 14-20 days Quality criteria for treatment:

Removal of orbital contents, absence of inflammatory symptoms, preservation of life.

Possible side effects and complications:

Tumor recurrence. Distant metastases.

Requirements for work, rest, and rehabilitation regimen:

Patients are disabled for 4-6 weeks. Further treatment.

Statement on absence of conflict of interest: none.

Reviewers:

1) Adylkhanov Tasbolat Adylkhanovich – Doctor of Medical Sciences, Head of the Department of Oncology and Visual Diagnostics of the State Medical University of Semey.

7.4 Indication of conditions for protocol revision:

Protocol revision 5 years after its publication and from the date of its entry into force or in the presence of new methods with evidence level.

Further Management: The goal of follow-up observation is: 1) prevention of complications (optic nerve atrophy, keratitis, corneal xerosis) with organ-preserving treatment; after orbital exenteration – prevention of secondary infection and bleeding; 2) early detection of metastases, tumor recurrence and timely referral to an oncologist at the Regional Oncology Dispensary.

13

Observation at the oncology dispensary with an oncological surgeon – once every 3 months during the first year (4 visits), then once every 6 months (twice a year); in cases of preserved eyeball, observation at the outpatient level at the place of residence with an ophthalmologist – once every 3 months during the first year (4 visits).

Follow-up observation of cured patients:

• during the first year after completion of treatment – once every 3 months;
• during the second year after completion of treatment – once every 6 months;
• from the third year after completion of treatment – once a year for 3 years.

Examination methods:

• local control – at each examination;
• palpation of regional lymph nodes – at each examination;
• radiographic examination of chest organs – once a year;
• ultrasound examination of abdominal organs – once every 6 months (for primary-advanced and metastatic tumors);
• observation by an oncologist at the place of residence (examination of the removed tumor area, palpation of peripheral lymph nodes);
• chest radiography – once every 3 months during the 1st year of observation; once every 6 months in the 2nd year of observation and once a year in the 3rd year.
• ultrasound of lymph nodes – once every 3 months during the 1st year of observation; once every 6 months in the 2nd year of observation and once a year in the 3rd year.

General contraindications for radiation therapy are:

• absence of morphological verification of diagnosis;
• presence of necrosis, tumor decay or bleeding from it, clinically and by

General indications for radiation therapy are:

17

• morphologically established diagnosis – malignant or benign tumor, after surgery or biopsy (open, stereotactic);
• with clinical diagnosis established on the basis of clinical-instrumental research methods (CT/MRI with contrast and/or PET-CT) without morphological verification due to impossibility of performing surgical treatment or tumor biopsy (open or stereotactic);
• for recurrences or continued tumor growth after previously performed combined or complex treatment where a radiation component was used.

Requirements for performing the procedure

Conditions for conducting treatment:

Personnel working in radiation therapy departments (radiological departments) of medical organizations providing oncological care to the population must have appropriate knowledge and qualifications confirmed by documents, and belong to Group A personnel. A radiation therapy physician (radiologist) must periodically undergo radiation safety courses. Compliance with all sanitary norms and radiation safety rules according to regulatory legal acts of the Republic of Kazakhstan is mandatory.

Requirements for equipment, consumables, medications:

• medical linear electron accelerators must be equipped with MLC (multi-leaf collimator) of at least 120 leaves, EPID system with detector panel resolution of 1024 x 768 pixels;
• medical linear electron accelerators must be equipped with MLC of at least 120 leaves, EPID system with detector panel resolution of 1024 x 768 pixels;
• X-ray simulator with possible CBCT function;
• computed tomography scanner with virtual simulation function and aperture of at least 80 cm with specially adapted flat table top;
• dosimetric planning system version not lower than Eclipse 10.0;
• Aria information management system;
• standard set of fixation and immobilization devices;
• standard set of dosimetric equipment.

Requirements for patient preparation for treatment:

IMRT is performed in inpatient or day hospital treatment conditions. There are no special conditions for patient preparation for the IMRT procedure.

Based on the biological model of radiation therapy's effect on the tumor, preoperative radiation therapy is theoretically justified. Irradiation reduces the biological activity of the tumor, promotes its devitalization, which significantly reduces the risk of local recurrence and metastases, creates favorable conditions for surgical intervention by increasing the ablasticity of the operation and tumor resectability (reduction of total tumor mass, formation of "pseudocapsule", increased mobility of the neoplasm). The total focal dose should be 40-50 Gy, single dose 4.5 Gy twice a week or 2 Gy daily.

18 The interval between surgery and the start of radiation should not exceed 3 weeks [10] (LE A).

The postoperative radiation zone should include the postoperative scar, residual tumor, or bed of the removed neoplasm. Postoperative radiation therapy is performed 2–3 weeks after formation of a complete postoperative scar, total dose 50–70 Gy, depending on the histological type of neoplasm [10] (LE A). The total dose of external beam radiotherapy depends on the stage of the neoplastic process and ranges from 40 to 70 Gy (1.5-1.8, 2 Gy per fraction) [10] (LE A). Conformal radiation therapy (3D-CRT) is a high-precision external beam radiation therapy technique based on determining the three-dimensional volume of the tumor and anatomy of critical organs. Conformal radiation therapy includes: 3D-CRT, IMRT (intensity-modulated radiation therapy); IGRT (image guided radiation therapy).

Conformal irradiation (3D-conformal irradiation or 3D-CRT), when the shape of the irradiated volume is maximally approximated to the shape (configuration) of the tumor. On one hand, precision (accuracy) of irradiation is achieved – when all parts of the tumor, which may have an irregular shape, fall within the irradiated volume, and on the other – selectivity – when irradiation of normal tissues and critical organs surrounding the tumor is limited (minimized). Critical organs are considered: eyeball (R and L), optic nerves (R and L), optic chiasm, pupils (R and L), brainstem and brain. To prevent critical organs from receiving a high radiation dose and to ensure the single dose does not exceed the maximum permissible dose when delivering a beam of high-energy X-rays to the tumor, critical organs were shielded by collimator leaves. Their tolerance is determined according to international protocols: RTOG/EORTC, TD5/5 and TD50/5, QUANTEC, etc. [48,54,63,66] (LE A).

Due to the combination of precision and selectivity with 3D-CRT, IMRT, IGRT, fewer radiation injuries to surrounding healthy tissues develop due to reduced radiation load on them compared to comparable doses with non-conformal (conventional) 2D irradiation [60] (LE A).

For proper conduct of 3D-CRT, IMRT, IGRT, appropriate treatment equipment is necessary, correct imaging of the primary tumor and surrounding structures obtained by CT or MRI, rigid immobilization of the patient on the simulation and treatment table, and consideration of possible physiological movement of organs and tissues [50,64] (LE A).

In conventional radiation therapy, simple irradiation techniques are used (rectangular radiation fields using standard blocks, boluses, wedges, etc.). During topometric preparation, selection of treatment field boundaries and center is performed based on projection onto the patient's skin, and radiation planning itself is more often performed based on one (central – at the level of the target midpoint) or less often – several transverse sections,

based on transverse computed tomography scans. The selected irradiation plan is verified on a simulator and implemented on external beam treatment units – a linear electron accelerator, which is preferable in children, or a gamma-therapeutic apparatus. The formation of the radiation field is performed using primary collimators of the units (linear accelerator or gamma-therapeutic apparatus), and the treatment field is formed using special (less commonly – individual) lead blocks, which protect (shield) normal organs and tissues.

Unlike conventional (2D) irradiation, conformal radiation therapy requires mandatory three-dimensional planning of the selected treatment volume, performed based on a package of computed or magnetic resonance tomograms taken with a 2-5 mm step. Improved 3D CRT, IMRT, IGRT plans compared to 2D irradiation can be characterized by the following comparative options: better indicators of uniformity of tumor irradiation of vital organs and/or reduction of radiation loads on vital organs and tissues.

The creation of a multileaf collimator (MLC) was also an improvement in equipment, allowing the leaves forming the radiation field to be moved by computer and creating fields of complex configuration corresponding to the tumor shape. A significant expansion of the technological approach is also the possibility of dynamically changing the configuration of the radiation field using MLC when changing irradiation directions, as well as implementing beam intensity modulation, i.e., conducting intensity-modulated radiation therapy (IMRT) [48,63,58,64] (LOE A).

The target volume was divided into three different volumes: (a) visible tumor, or gross tumor volume (GTV), (b) clinical target volume (CTV) – the volume of GTV + microscopic tumor spread, and (c) planning target volume (PTV) – CTV + volume to account for geometric errors and other factors. GTV and CTV are clinical-anatomical concepts that are determined before selecting the treatment method and technique. PTV is determined by specifying specific fields that are added around the CTV to control organ, tumor, and patient displacement or movement, inaccuracies in radiation beam settings and/or patient fixation, and any other uncertainty factors. PTV is a static value, and this geometric concept is used for treatment planning and dose specifications. The size and configuration of PTV directly depend on the GTV/CTV volume and effects caused by organ and tumor movements, technical aspects of the treatment technique (e.g., patient fixation) [66,53,54,55,48] (LOE A).

Preparation and conduct of 3D CRT, IMRT, IGRT:

After deciding on the need to use radiation therapy in a patient, X-ray computed and/or magnetic resonance tomograms are analyzed, which reflect the maximum extent of the tumor process – as fundamental data for the planned treatment process. Using CT and/or MRI, the condition (dynamics during previous treatment, if performed) of the tumor at the time of irradiation is also clarified. The possibility of three-dimensional modeling allows fairly accurate determination of the volumes and mutual arrangement of the tumor and surrounding normal organs and tissues, including organs at risk.

During pre-radiation preparation, the position and size of the tumor and surrounding organs and tissues are determined on X-ray simulators and CT or less commonly MRI. Due to age or restless behavior, some patients require medicated sleep for better fixation and reproduction of body position during subsequent treatment. Using light and laser centering, reference marks are placed on the patient's body, which will subsequently be used for positioning during irradiation sessions. Reproducibility of the same patient position during all preparation and treatment procedures is important, which is facilitated by various fixation devices. Images obtained when scanning the irradiation area are sent to the planning system, on which, based on irradiation specifications (volumes, irradiation goals, single and total doses, fractionation regimens, organs at risk, etc.), irradiation parameters are determined (type and energy of radiation, size, directions and number of beams, etc.) and dose distribution is calculated, as well as the feasibility of using protective blocks, collimators and compensators (to shield normal tissues).

After preparing the treatment program, verification (simulation) of the selected irradiation plan is performed on the treatment apparatus – the patient's irradiation conditions are reproduced under visual control of the irradiated area using X-ray simulators or CT simulators. Simulation of the irradiation process allows comparison of the selected computer irradiation plan with the actual treatment process and, if necessary, its correction. After approval of the treatment plan, the course of radiation therapy begins. Considering that irradiation is most often conducted over 2-6 weeks, verification of treatment parameters and, if necessary, correction are performed repeatedly.

Orbital sarcomas are poorly sensitive to radiation therapy. In rare cases, RT may be used for palliative purposes to reduce pain syndrome and temporarily slow tumor progression.

In the complex treatment of sarcomas in adults, this tumor is less sensitive to ionizing radiation, so the total dose should be at least 70 Gy.

Despite the high effectiveness of the combined method of treating malignant orbital sarcomas (5-year survival reaches 93%), up to 10% of rhabdomyosarcomas may be refractory to both chemo- and radiation therapy.