Experience of stereotactic radiation therapy and radiosurgical treatment of metastatic vertebral tumors Текст научной статьи по специальности «Клиническая медицина»

South Russian Journal of Cancer. 2024. Vol. 5, No. 2. P. 6-13

4.0

https://doi.org/10.37748/2686-9039-2024-5-2-1

https://elibrary.ru/gjahux

South Russian

Journal of Cancer

ORIGINAL ARTICLE

Южно-Российский

онкологический журнал

Vol. 5

Experience of stereotactic radiation therapy and radiosurgical No. 2, 2024

treatment of metastatic vertebral tumors

O. I. Kit, D. E. Zakondyrin, E. E. Rostorguev, P. G. Sakun, V. I. Voshedskii, M. A. Komandirov National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation russiandoctor@mail.ru

ABSTRACT

Purpose of the study. Evaluation of the effectiveness of extracranial stereotactic radiation therapy in various fractionation regimens in the treatment of patients with metastatic vertebral lesions.

Patients and methods. The study included 12 patients with metastatic spinal lesions who underwent extracranial stereotactic radiation therapy (SBRT) on a Novalis Tx linear accelerator, Varian, in radiosurgery mode (SRS; in 1 fraction) and hypofractionation mode (SFD 5Gy, TFD 25Gy, 5 fractions) in the period from 01/01/2020 to 03/31/2022. The assessment of local control was carried out using positron emission tomography – computed tomography (PET-CT) from 18FDG. The intensity of the pain syndrome before and after radiation was assessed using a visual analog pain scale (VAS).

Results. 19 vertebrae with metastatic lesions were irradiated in 12 patients. The SBRT technique in hypofractionation mode was used in 6 (50 %) patients, in radiosurgery (SRS) mode was used in 4 (34 %) patients, in 2 (17 %) patients a combination of irradiation techniques was used on various affected segments of the spinal column. The general tumor volume (GTV) averaged 30.56 = 7.8 km2. When using the radiosurgical irradiation regimen, SFD ranged from 16 to 18 Gy. When using the hypofractionation technique, the total focal dose (TFD) was 25 Gy, a single focal dose (SFD) was 5 Gy.

Conclusion. Stereotactic radiation therapy and radiosurgery of metastatic vertebral tumors without compression of neural structures provides local tumor control in 92 % of patients within 6 months and in 83 % of patients within 1 year, regression of pain after irradiation – in 67 % of patients.

Keywords: stereotactic radiotherapy, radiosurgery, spinal metastases For citation: Kit O. I., Zakondyrin D. E., Rostorguev E. E., Sakun P. G., Voshedskii V. I., Komandirov M. A. Experience of stereotactic radiation therapy and radiosurgical treatment of metastatic vertebral tumors. South Russian Journal of Cancer. 2024; 5(2): 6-13.

https://doi.org/10.37748/2686-9039-2024-5-2-1, https://elibrary.ru/gjahux For correspondence: Dmitry E. Zakondyrin – Cand. Sci. (Med.), PhD student of the Department of Neurological Oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation Address: 63 14 line str., Rostov-on-Don 344037, Russian Federation E-mail: russiandoctor@mail.ru

ORCID: https://orcid.org/0000-0002-0925-415X

SPIN: 7298-0181, AuthorID: 703429

Compliance with ethical standards: This research has been carried out in compliance with the ethical principles set forth by the World Medical Association Declaration of Helsinki, 1964, ed. 2013. The study was approved by the Committee on Biomedical Ethics at the National Medical Research Center of Oncology, the Russian Federation Ministry of Health (extract from the protocol of the meeting No. 118 dated 06/02/2022).

Informed consent was received from all the participants of the study Funding: this work was not funded

Conflict of interest: Kit O. I. has been the member of the editorial board of the South Russian Journal of Cancer since 2019, however he has no relation to the decision made upon publishing this article. The article has passed the review procedure accepted in the journal. The authors did not declare any other conflicts of interest

The article was submitted 03.10.2023; approved after reviewing 09.04.2024; accepted for publication 09.05.2024

© Kit O. I., Zakondyrin D. E., Rostorguev E. E., Sakun P. G., Voshedskii V. I., Komandirov M. A., 2024

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Южно-Российский онкологический журнал. 2024. Т. 5, № 2. С. 6-13

https://doi.org/10.37748/2686-9039-2024-5-2-1

https://elibrary.ru/gjahux

3.1.6. Онкология, лучевая терапия

ОРИГИНАЛЬНАЯ СТАТЬЯ

Опыт стереотаксической лучевой терапии и радиохирургического лечения

метастатических опухолей позвонков

О. И. Кит, Д. Е. Закондырин, Э. Е. Росторгуев, П. Г. Сакун, В. И. Вошедский, М. А. Командиров

ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения Российской Федерации, г. Ростов-на-Дону, Российская Федерация

russiandoctor@mail.ru

РЕЗЮМЕ

Цель исследования. Оценка эффективности экстракраниальной стереотаксической лучевой терапии в различных

режимах фракционирования при лечении пациентов с метастатическим поражением позвонков

Пациенты и методы. В исследование включено 12 больных c метастатическим поражением позвоночника, которым

была проведена экстракраниальная стереотаксическая лучевая терапия (SBRT) на линейном ускорителе Novalis Tx, Varian, в режиме радиохирургии (SRS; за 1 фракцию) и режиме гипофракционирования (разовая очаговая доза (РОД) 5Гр, суммарная очаговая доза (СОД) 25Гр, 5 фракций) в период с 01.01.2020 по 31.03.2022 гг. Оценка локального

контроля осуществлялась с использованием позитронно- эмиссионной томографии – компьютерной томографии

(ПЭТ-КТ) с 18ФДГ. Интенсивность болевого синдрома до и после облучения оценивали по визуально аналоговой

шкале боли (ВАШ).

Результаты. У 12 пациентов проведено облучение 19 метастатических пораженных позвонков. Методика SBRT

в режиме гипофракционирования была применена у 6 (50 %) больных, в режиме радиохирургии (SRS) использована

у 4 (34 %) пациентов, у 2 (17 %) больных на различных пораженных сегментах позвоночного столба применялась

комбинация методик облучения. Общий объем опухоли (GTV) в среднем составлял 30,56 ± 7,8 см². При применении

радиохирургического режима облучения РОД составляла от 16 до 18Гр. При применении методики гипофракционирования СОД составила 25 Гр, РОД – 5 Гр.

Заключение. Экстракраниальная стереотаксическая лучевая терапия метастатических опухолей позвонков без

компрессии невральных структур обеспечивает локальный контроль опухоли у 92 % больных в течение 6 месяцев

и у 83 % пациентов в течение 1 года, регресс болевого синдрома после облучения – у 67 % больных.

Ключевые слова: стереотаксическая лучевая терапия, радиохирургия, метастазы в позвоночник

Для цитирования: Кит О. И., Закондырин Д. Е., Росторгуев Э. Е., Сакун П. Г., Вошедский В. И., Командиров М. А. Опыт стереотаксической

лучевой терапии и радиохирургического лечения метастатических опухолей позвонков. Южно-Российский онкологический журнал. 2024; 5(2): 6-13. https://doi.org/10.37748/2686-9039-2024-5-2-1, https://elibrary.ru/gjahux Для корреспонденции: Закондырин Дмитрий Евгеньевич – к.м.н., докторант отделения нейроонкологии, ФГБУ «Национальный

медицинский исследовательский центр онкологии» Министерства здравоохранения Российской Федерации, г. Ростов-на-Дону, Российская Федерация

Адрес: 344037, Российская Федерация, г. Ростов-на-Дону, ул. 14-я линия, д. 63

E-mail: russiandoctor@mail.ru

ORCID: https://orcid.org/0000-0002-0925-415X

SPIN: 7298-0181, AuthorID: 703429

Соблюдение этических стандартов: в работе соблюдались этические принципы, предъявляемые Хельсинкской декларацией Всемирной

медицинской ассоциации (World Medical Association Declaration of Helsinki, 1964, ред. 2013). Исследование одобрено Комитетом по

биомедицинской этике при ФГБУ «Национальный медицинский исследовательский центр онкологии» Министерства здравоохранения

Российской Федерации (выписка из протокола заседания № 118 от 02.06.2022 г.). Информированное согласие получено от всех

участников исследования.

Финансирование: финансирование данной работы не проводилось

Конфликт интересов: Кит О. И. является членом редакционной коллегии журнала «Южно-Российский онкологический журнал» с 2019 г., но

не имеет никакого отношения к решению опубликовать эту статью. Статья прошла принятую в журнале процедуру рецензирования. Об иных

конфликтах интересов авторы не заявляли

Статья поступила в редакцию 03.10.2023; одобрена после рецензирования 09.04.2024; принята к публикации 09.05.2024

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Kit O. I., Zakondyrin D. E., Rostorguev E. E., Sakun P. G., Voshedskii V. I., Komandirov M. A. Experience of stereotactic radiation therapy and radiosurgical treatment of metastatic vertebral tumors

INTRODUCTION

an irradiation field of a given shape with minimal

impact on surrounding tissues. The possibility of

An analysis of the literature shows that 30–50 %

concentrating the radiation dose without increasing

of cancer patients have metastatic spinal column

it during conformal radiation therapy in the tumor

lesions, including 70–80 % of patients with breast

area is, among other things, a way to overcome its

or prostate cancer and 40 % of patients with ad-

radioresistance. Stereotactic body radiation therapy

vanced lung cancer [1]. In one third of patients, the

(SBRT) and radiosurgery (SRS) have taken leading

lesion of the vertebrae is symptomatic. Clinical

positions among conformal methods in the treat-

manifestations are most often represented by pain

ment of spinal tumors. In stereotactic radiation

syndrome, varying in intensity. For a long time, con-

therapy, tumor destruction occurs in several large

ventional radiation therapy (CRT) has been used in

fractions (5–12 Gy each), in stereotactic radiosur-

the treatment of this group of patients and in the

gery – by summing up a radical dose (15–21 Gy) in

absence of indications for surgical treatment, which

one session.

has a satisfactory (up to 80 % of cases) analgesic

The purpose of the study was to evaluate the

effect, however, local relapses occur in 60–80 % of

effectiveness of extracranial stereotactic radia-

patients, and the analgesic effect often develops

tion therapy in various fractionation regimes in

only 2–3 weeks after treatment, especially with ra-

the treatment of patients with metastatic vertebral

dioresistant tumors [2]. Currently, conformal meth-

lesions.

ods of radiation therapy in the treatment of bone

metastases are replacing conventional radiation

PATIENTS AND METHODS

therapy, despite their disadvantages in the form of

the need for longer patient preparation, additional

The study included 12 patients with metastatic

diagnostic studies, and high cost [3]. The main dif-

spinal lesions who underwent extracranial stereo-

ference between conformal radiation therapy and

tactic radiation therapy (SBRT) on a Novalis Tx linear

conventional radiation therapy is the creation of

accelerator, Varian, in radiosurgery mode (SRS; for

Table 1. Characteristics of metastatic vertebral tumors in patients Indicator

Indicator value ( n = 19)

The location of a metastatic tumor in the spine according to the Tomita classification 1 type

4 (21 %)

5 type

1 (5 %)

7 type

14 (74 %)

Localization of the tumor in the vertebra

body

13 (68 %)

body + peduncle of the arch

3 (16 %)

total defeat

3 (16 %)

The degree of tumor spread according to the Weinstein-Boriani classification В + С

18 (95 %)

А + В + С

1 (5 %)

Level of lesion

Cervical

2 (10.5 %)

Thoracic

7 (37 %)

Lumbar

8 (42 %)

Sacral

2 (10 %)

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Южно-Российский онкологический журнал 2024. Т. 5, № 2. С. 6-13

Кит О. И., Закондырин Д. Е., Росторгуев Э. Е., Сакун П. Г., Вошедский В. И., Командиров М. А. Опыт стереотаксической лучевой терапии

и радиохирургического лечения метастатических опухолей позвонков

1 fraction) and hypofractionation mode (SFD 5Gy,

scale averaged 5.0 ± 0.59 points. All patients were

TFD 25Gy, 5 fractions) in the period from 01/01/2020

neurologically intact (Frankel type E) and functionally

to 03/31/2022.

intact (70–80 points according to Karnofsky). Pain

The average age of the patients was 55.47 ± 2.89

syndrome before the course of radiation occurred in

years, the ratio of men and women was 2:10. Grade

all patients, the average score according to VAS was

1b epidural compression was detected in only 1 pa-

5.4 ± 0.67. According to the histological type of the

tient. The stability of the spinal column on the SINS

primary tumor, the distribution was as follows: breast

A

B

C

D

Fig. 1. Assessment of local control after radiation therapy in patient L-o. A, B – MRI and CT data of the thoracic spine before treatment (signs of metastatic lesion of the Th3 vertebra); C – data of the control PET-CT during the observation period 3 months after irradiation (there are no signs of pathological activity in the irradiation zone); D – data of the control PET-CT during the observation period after 12 months after irradiation (signs of recurrence of formation in the area of the vertebral arch peduncle) 9

South Russian Journal of Cancer 2024. Vol. 5, No. 2. P. 6-13

Kit O. I., Zakondyrin D. E., Rostorguev E. E., Sakun P. G., Voshedskii V. I., Komandirov M. A. Experience of stereotactic radiation therapy and radiosurgical treatment of metastatic vertebral tumors

cancer – 10 (84 %) patients, skin melanoma – 1 (8 %)

used, the intensity of pain syndrome was assessed

patient, without an established primary focus –

using a visually analog pain scale (VAS), and the

1 (8 %) patient. The characteristics of metastatic

SINS scale was used to assess instability in the af-

vertebral tumors in patients with neuroimaging are

fected spinal- motor segment. All patients were ex-

represented in Table 1.

amined on the day of admission, at discharge and

The general tumor volume (GTV) averaged

every 3 months after completion of the course of

30.56 ± 7.8 cm2. The average radiation dose for

radiation therapy. All patients underwent computed

single- fraction courses was 26 [13; 16] Gy. When

tomography (CT) and magnetic resonance imaging

using the hypofractionation technique, the average

(MRI) of the spinal column before treatment, postop-

total focal dose (TFD) was 25 [25; 26] Gy, the average

erative assessment of local control was carried out

single focal dose (SFD) was 5 [5; 8] Gy.

using positron emission tomography – computed

A single metastatic lesion in the spine at the be-

tomography (PET-CT) with 18F-fluorodeoxyglucose

ginning of treatment was observed in 2 (17 %) pa-

(18-FDG) (Fig. 1).

tients, in the remaining patients metastatic lesion of

The irradiation was carried out on the Novalis Tx

the vertebrae was of a multiple nature. In addition

linear accelerator, Varian. Topometric tomography

to the spine, 6 (50 %) had metastasis to other flat

was previously performed on a Siemens Somatom

bones of the skeleton, and 4 (34 %) had visceral me-

computed tomograph, and preliminary topometry

tastases.

was processed at the Singo Via virtual simula-

To assess the neurological status and condition

tion station. A full-body vacuum mattress with an

of patients, the Frankel and Karnofsky scales were

ArmShuttle board was used for immobilization and

A

B

C

D

Fig. 2. Radiation planning. A – anatomical segmentation and contouring of critical organs and structures; B – delineation of the GTV volume from images of various modalities and formation of the CTV volume; C – сontouring of the spinal cord and the formation of PTV volume; D – dosimetry planning with control of target coverage and load on critical organs and structures, followed by analysis of the calculated irradiation plan

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Южно-Российский онкологический журнал 2024. Т. 5, № 2. С. 6-13

Кит О. И., Закондырин Д. Е., Росторгуев Э. Е., Сакун П. Г., Вошедский В. И., Командиров М. А. Опыт стереотаксической лучевой терапии

и радиохирургического лечения метастатических опухолей позвонков

reproducibility of the patient's laying. Using the Ele-

irradiation techniques were used in 2 (17 %) patients

ments Brainlab software, segmentation, contouring

on various affected segments of the spinal column.

and formation of a 3D treatment plan for a linear

The radiation therapy performed was part of the

accelerator were performed. The laying and con-

complex treatment in 10 (83 %) patients, combined –

trol of the patient's position were performed using

in 2 (17 %).

orthogonal X-rays using the ExacTrac X-Ray Moni-

The average duration of follow-up was

toring BrainLab positioning system. Verification of

12.18 ± 2.23 months. Radiological local control

the calculated stereotactic radiotherapy treatment

(complete, partial response and stabilization of

plan was carried out on a StereoPHAN phantom with

the disease according to the RECIST criteria) was

a matrix of SRS Mapcheck detectors. Before the

achieved in 11 (92 %) patients within 6 months, in 10

radiosurgical treatment session, the absolute dose

(83 %) – within 1 year. Progression of the underlying

calibration of the accelerator and the calibration

disease during the follow-up period was noted in

of the positioning system were checked. The dose

6 (50 %) patients. The average survival rate before

was delivered using a dynamic volume modulated

progression was 9.11 ± 2.69 months. A decrease

technique (VMAT).

in back pain after irradiation was noted by 8 (67 %)

The clinical volume of the tumor (CTV) was

patients, there were no cases of an increase in pain

determined in accordance with the International

syndrome.

Spine Radiosurgery Consortium Consensus Guide-

lines [4]. The planned tumor volume (PTV) was cal-

DISCUSSION

culated by adding a 2 mm edge to the CTV bound-

aries, minus the PRV (planning risk volume) for

Stereotactic radiation therapy and radiosurgery

the spinal cord (+ 3 mm to the edge of the spinal

show high efficiency in the treatment of metastatic

cord in all directions) and taking into account the

tumors of the vertebrae. One of the primary goals of

location of the risk organs (oropharynx, esopha-

irradiation of tumors that do not compress the spinal

gus, etc.) (Fig. 2).

cord is the treatment of pain syndrome. Vargo J. A.

For each group of indicators, the type of data dis-

et al. [5] It is proposed to apply certain modes of irra-

tribution was determined (histogram construction

diation, depending on the purpose of the treatment.

according to the Kolmogorov – Smirnov test). If the

If the main task is to relieve pain, then preference is

application of the criterion showed a normal dis-

given to radiation for 1 fraction (16–18 Gy). In order

tribution of data, the average, the error of the aver-

to achieve long-term local control, preference is giv-

age (M ± m) was used for the description. When the

en to fractionated SBRT modes (8–9 Gy × 3 fr., or

distribution differs from the normal law, the values

6–7 G × 5 fr.).

of the median, 1st and 3rd quartiles (Me [Q1; Q3])

Randomized studies of the analgesic effect

were used for the description. The threshold level of

of radiation therapy performed in patients using

significance for testing statistical hypotheses was

single- fraction SBRT (16–18 or 24 Gy) and mono-

assumed to be 0.05.

multi- fraction CRT (8 Gy for 1 fraction or 30 Gy for

10 fractions) showed no significant difference be-

STUDY RESULTS

tween the groups of patients 3 months after treat-

ment, and a significantly better effect of SBRT after

In 12 patients, 19 metastatic vertebral tumors

6 months [6, 7]. The limitation of these studies was

were irradiated.

the lesion of no more than 2 adjacent vertebrae

The majority of patients (80 %, n = 10) underwent

and the presence of a distance of at least 3 mm

1 course of radiation therapy, 20 % of patients re-

between the edge of the tumor and the spinal cord

ceived 2 courses of radiation. At the same time, ir-

(no more than 1b degree ESCC), otherwise the

radiation of one vertebra was performed in 8 (67 %)

groups could not be randomized. Sahgal A. and

patients, 4 (33 %) received irradiation of two or more

co-author. [8] In the course of a randomized multi-

segments of the spinal column. The SBRT technique

center study, the advantages of SBRT (two-fraction

was used in 6 (50 %) patients, radiosurgery (SRS)

24 Gy) over CRT (20 Gy in 5 fractions) in effective-

was used in 4 (34 %) patients. Both SBRT and SRS

ness against pain syndrome in metastatic spinal in-

11

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Kit O. I., Zakondyrin D. E., Rostorguev E. E., Sakun P. G., Voshedskii V. I., Komandirov M. A. Experience of stereotactic radiation therapy and radiosurgical treatment of metastatic vertebral tumors

jury were also noted, even during the first 3 months

the follow-up period, progression was noted in 50 %

after treatment. The results of randomized stud-

of patients, while local control was achieved by the

ies comparing the effectiveness of CRT and SBRT

end of the first year after completion of the radiation

techniques in relation to local tumor control are

course in 83 %.

currently not available in the literature. Meta-anal-

ysis conducted by Singh R. et al. [9], which included

CONCLUSION

3237 patients, showed the presence of local tumor

control in 92.9 % of patients after single- factional

Stereotactic radiation therapy and radiosurgery of

SBRT (RS) versus 81 % after CRT or 82.1 % after

metastatic vertebral tumors without compression of

multi- factional CRT.

neural structures provides local tumor control in 92 %

Local radiation does not prevent the progression

of patients for 6 months. and in 83 % of patients

of the underlying disease, so it should be used in

within 1 year, regression of pain syndrome after ir-

combination with chemotherapy treatment. During

radiation – in 67 % of patients.

References

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7. Ryu S, Deshmukh S, Timmerman R, Movsas B, Gerszten P, Yin F, et al. Radiosurgery Compared To External Beam Radiotherapy for Localized Spine Metastasis: Phase III Results of NRG Oncology/RTOG 0631. Int J Radiat Oncol Biol Phys. 2019

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Information about authors:

Oleg I. Kit – Academician at the Russian Academy of Sciences, Dr. Sci. (Med.), professor, general director, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0003-3061-6108, SPIN: 1728-0329, AuthorID: 343182, ResearcherID: U-2241-2017, Scopus Author ID: 55994103100

Dmitry E. Zakondyrin – Cand. Sci. (Med.), PhD student of the Department of Neurooncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0002-0925-415X, SPIN: 7298-0181, AuthorID: 703429

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Южно-Российский онкологический журнал 2024. Т. 5, № 2. С. 6-13

Кит О. И., Закондырин Д. Е., Росторгуев Э. Е., Сакун П. Г., Вошедский В. И., Командиров М. А. Опыт стереотаксической лучевой терапии

и радиохирургического лечения метастатических опухолей позвонков

Eduard E. Rostorguev – Dr. Sci. (Med.), head of the Department of Neurological Oncology, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0003-2937-0470, SPIN: 8487-9157, AuthorID: 794808, Scopus Author ID: 57196005138

Pavel G. Sakun – Cand. Sci. (Med.), head of Radiotherapy Department No. 2, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0001-8061-6259, SPIN: 3790-9852, AuthorID: 734600, Scopus Author ID: 56531945400

Vitalii I. Voshedskii – Cand. Sci. (Med.), radiotherapist of Radiotherapy Department No. 2, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0000-0003-1405-8329, SPIN: 4732-4005, AuthorID: 1032685, ResearcherID: Q-6122-2019, Scopus Author ID: 57215970384

Maksim A. Komandirov – medical physicist at the Radiotherapy Department No. 2, National Medical Research Centre for Oncology, Rostov-on-Don, Russian Federation

ORCID: https://orcid.org/0009-0008-0273-9737, SPIN: 9331-1278, AuthorID: 843316, Scopus Author ID: 36952848600

Contribution of the authors:

Kit O. I. – performed development of the research design, critical revision with the introduction of valuable intellectual content, final approval of the published version of the manuscript;

Zakondyrin D. E. – contributed to the research design development, analysis of the obtained data, writing the text of the manuscript; Rostorguev E. E. – review of publications on the topic of the article, a set of clinical material, interpretation of the results; Sakun P. G. – performed data collection, analysis and interpretation, technical editing; Voshedskii V. I. – took part in research design development, analysis of the data obtained; Komandirov M. A. – contributed to the data collection, interpretation, technical editing.

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