Improvement of long-term treatment results in oligometastatic colorectal cancer patients by using a combined approach Текст научной статьи по специальности «Клиническая медицина»

South Russian Journal of Cancer. 2024. Vol. 5, No. 4. P. 20-28 4.0

https://doi.org/10.37748/2686-9039-2024-5-4-3

https://elibrary.ru/cctlum

South Russian

Journal of Cancer ORIGINAL ARTICLE

Южно-Российский

онкологический журнал

Vol. 5

No. 4, 2024 Improvement of long-term treatment results in oligometastatic

colorectal cancer patients by using a combined approach

E. O. Kalmykova1, R. V. Ishchenko1,2, O. Yu. Stukalova3, D. A. Filimonov2

1 Lomonosov Moscow State University, Moscow, Russian Federation

2 V. K. Gusak institute of emergency and reconstructive surgery, Donetsk, Russian Federation

3 ALLORO Medical Center, Fryazino, Russian Federation

 [email protected]

ABSTRACT

Purpose of the study. To improve the treatment results of patients suffering from CRC with oligometastatic lesion by deter-

mining the most effective combination of treatment methods.

Patients and methods. The results of treatment of 71 patients with oligometastases of colorectal cancer were analyzed.

All patients were divided into 2 groups depending on the treatment methods. The first group included 35 patients who un-

derwent simultaneous removal of the primary tumor and metastatic foci at the first stage of complex treatment. The second

group includes clinical data on 36 patients who underwent primary lesion removal at the first stage of complex treatment

followed by drug antitumor therapy.

Results. In the primary tumor removal group, the response was received in 3 (8.3 %) cases, stabilization was achieved in

14 (38.9 %) cases, and progression of the tumor process was detected in 19 (52.8 %) cases. The median disease-free sur-

vival was 9.2 ± 3.2 months. One-year, two- and three-year survival rates in the group of simultaneous removal of the primary

tumor and oligometastases and in the group of primary tumor removal were 97.1 %, 88.6 %, 77.1 % and 100 %, 80.5 %, 72.2 %,

respectively. The overall survival rate in the group of simultaneous removal of the primary tumor and oligometastases was

63 ± 3.9 months, in the group of primary tumor removal – 58 ± 3.8 months.

Conclusion. In the presented clinical study, a comparative assessment of the effectiveness of the treatment of patients with

colorectal cancer with oligometastases was carried out, depending on the option of an integrated approach. The results

obtained turned out to be multidirectional – the response to treatment and progression were obtained in 54.3 % and 45.7 %

of cases in the group of simultaneous removal of the primary tumor and oligometastases versus 47.2 % and 52.8 % of cases

in the group of removal of the primary tumor without oligometastases, respectively. The median recurrence-free survival was

shorter in the group of primary tumor removal without metastases. Complete removal of the primary tumor and oligometas-

tases can significantly increase the overall survival rates of patients.

Keywords: colorectal cancer, oligometastases, chemotherapy, lung metastases, liver metastases

For citation: Kalmykova E. O., Ishchenko R. V., Stukalova O. Yu., Filimonov D. A. Improvement of long-term treatment results in oligometastatic colorectal

cancer patients by using a combined approach. South Russian Journal of Cancer. 2024; 5(4): 20-28. https://doi.org/10.37748/2686-9039-2024-5-4-3,

https://elibrary.ru/cctlum

For correspondence: Elmira O. Kalmykova – MD, oncologist, Department of Antitumor Drug Therapy, Lomonosov Moscow State University, Moscow,

Russian Federation

Address: 27 Lomonosovsky Prospekt, bldg. 10, Moscow 119992, Russian Federation

E-mail: [email protected]

Compliance with ethical standards: the study was 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 V. K. Gusak institute of emergency and reconstructive

surgery, Donetsk, Russian Federation (extract from the protocol of meeting No. 2 dated 05/17/2024). Informed consent was received from all participants of

the study

Acknowledgement: the authors consider it their duty to express gratitude to Irina Ivanovna Selezneva, PhD., Head of the Department of antitumor Drug

therapy at the Central Research Hospital "RZD-Medicine" for valuable comments in the process of carrying out the scientific and practical part of the work

and comprehensive support

Funding: this work was not funded

Conflict of interest: the authors declare that there are no obvious and potential conflicts of interest associated with the publication of this article

The article was submitted 26.05.2024; approved after reviewing 01.11.2024; accepted for publication 14.11.2024

© Kalmykova E. O., Ishchenko R. V., Stukalova O. Yu., Filimonov D. A., 2024

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Южно-Российский онкологический журнал. 2024. Т. 5, № 4. С. 20-28

https://doi.org/10.37748/2686-9039-2024-5-4-3

https://elibrary.ru/cctlum

3.1.6. Онкология, лучевая терапия

ОРИГИНАЛЬНАЯ СТАТЬЯ

Улучшение отдаленных результатов лечения больных олигометастатическим

колоректальным раком путем применения комбинированного подхода

Э. О. Калмыкова1, Р. В. Ищенко1,2, О. Ю. Стукалова3, Д. А. Филимонов2

1 Московский государственный университет имени М. В. Ломоносова, г. Москва, Российская Федерация

2 ФГБУ «Институт неотложной и восстановительной хирургии имени В. К. Гусака» Министерства здравоохранения Российской Федерации,

г. Донецк, Российская Федерация

3 Медицинский центр «АЛЛОРО», г. Фрязино, Российская Федерация

 [email protected]

РЕЗЮМЕ

Цель исследования. Улучшить результаты лечения больных, страдающих колоректальным раком (КРР) с олигоме-

тастатическим поражением, за счет определения наиболее эффективной комбинации методов лечения.

Пациенты и методы. Проведен анализ результатов лечения 71 пациента с олигометастазами КРР. Все больные

были разделены на 2 группы в зависимости от методов лечения. В первую группу включены 35 больных, которым

на первом этапе комплексного лечения проводилось одномоментное удаление первичной опухоли и метастатиче-

ских очагов, с последующим проведением химиотерапии. Во вторую группу включены клинические данные о 36

больных, которым на первом этапе комплексного лечения проводилось удаление первичного очага с последующим

проведением лекарственной противоопухолевой терапии.

Результаты. В группе удаления первичной опухоли ответ получен в 3 (8,3 %) случаях, стабилизация достигнута

в 14 (38,9 %) случаях, в 19 (52,8 %) случаях выявлено прогрессирование опухолевого процесса. Медиана безрецидив-

ной выживаемости составила 9,2 ± 3,2 мес. Годичная, двух- и трехлетняя выживаемость в группе одномоментного

удаления первичной опухоли и олигометастазов и в группе удаления первичной опухоли составила 97,1, 88,6, 77,1

и 100, 80,5, 72,2 % соответственно. Общая выживаемость в группе одномоментного удаления первичной опухоли

и олигометастазов составила 63 ± 3,9 мес., в группе удаления первичной опухоли – 58 ± 3,8 мес.

Заключение. В представленном клиническом исследовании проводилась сравнительная оценка эффективности

проводимого лечения больных КРР с олигометастазами в зависимости от варианта комплексного подхода. Полу-

ченные результаты оказались разнонаправленными – ответ на лечение и прогрессирование получены в 54,3 и 45,7 %

случаях в группе одномоментного удаления первичной опухоли и олигометастазов против 47,2 и 52,8 % случаев

в группе удаления первичной опухоли без олигометастазов соответственно. Медиана безрецидивной выживаемости

оказалась короче в группе удаления первичной опухоли без метастазов. Удаление олигометастазов увеличивает

общую выживаемость, но результаты не достигают статистической значимости.

Ключевые слова: колоректальный рак, олигометастазы, химиотерапия, метастазы в легком, метастазы в печени

Для цитирования: Калмыкова Э. О., Ищенко Р. В., Стукалова О. Ю., Филимонов Д. А. Улучшение отдаленных результатов лечения больных

олигометастатическим колоректальным раком путем применения комбинированного подхода. Южно-Российский онкологический журнал. 2024;

5(4): 20-28. https://doi.org/10.37748/2686-9039-2024-5-4-3, https://elibrary.ru/cctlum

Для корреспонденции: Калмыкова Эльмира Олеговна – врач-онколог отделения противоопухолевой лекарственной терапии, Московский

государственный университет имени М. В. Ломоносова, г. Москва, Российская Федерация

Адрес: 119992, Российская Федерация, г. Москва, Ломоносовский проспект, д. 27, корп. 10

E- mail: [email protected]

ORCID: https://orcid.org/0009-0008-5842-1250

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 «Институт неотложной и восстановительной хирургии имени В. К. Гусака» Министерства здравоохранения

Российской Федерации (выписка из протокола заседания № 2 от 17.05.2024 г.). Информированное согласие получено от всех участников

исследования

Благодарности: авторы считают своим долгом выразить слова благодарности к.м.н., заведующей отделением противоопухолевой лекарственной

терапии ЧУЗ ЦКБ «РЖД- Медицина» Селезневой Ирине Ивановне за ценные замечания в процессе осуществления научной и практической части

работы и всестороннюю поддержку

Финансирование: финансирование данной работы не проводилось

Конфликт интересов: все авторы заявляют об отсутствии явных и потенциальных конфликтов интересов, связанных с публикацией настоящей статьи

Статья поступила в редакцию 26.05.2024; одобрена после рецензирования 01.11.2024; принята к публикации 14.11.2024

21

South Russian Journal of Cancer 2024. Vol. 5, No. 4. P. 20-28

Kalmykova E. O., Ishchenko R. V., Stukalova O. Yu., Filimonov D. A. Improvement of long-term treatment results in oligometastatic colorectal cancer patients by using

a combined approach

BACKGROUND years, a surgical treatment method has been actively

introduced, thanks to which the 5-year survival rate

Colon cancer (CC) is one of the leading oncolog- has increased to 58 % [13].

ical diseases not only in the Russian Federation but For a long time, specialists have been faced with

in worldwide as well. According to GLOBOCAN 2020 the question of whether to remove the primary tu-

data, colorectal cancer ranks third among the male mor in the presence of distant metastases or to lim-

and second among the female population in terms it themselves only to chemotherapeutic treatment.

of the number of cases [1]. Of the 100 new cases of M.Karoui noted in his work that the removal of the

colon cancer, more than 70 % of deaths from this dis- primary focus is very important, since this leads to

ease are recorded, mainly due to the late treatment an improvement in the quality of life of patients, pre-

of patients to a doctor. Since the tumor is located in venting possible complications such as intestinal

a hollow organ, the formation should be of significant obstruction, bleeding, peritonitis. Subsequent che-

size before the first symptoms appear. This occurs motherapy courses are more targeted [14]. However,

mainly when the tumor grows deeply into the sur- according to a study that compared patients who

rounding tissues [2]. underwent first-line primary tumor resection followed

The most common localization of oligometasta- by chemotherapy (144 patients, resection group)

ses of colorectal cancer are liver, lung, abdominal or those who underwent first-line chemotherapy

lymph nodes, ovaries, peritoneum. According to the (83 patients, chemotherapy group). In the resection

literature, there are isolated cases of metastasis to group, the incidence of intestinal obstruction, perito-

the spleen, adrenal glands and thyroid gland [3–8]. nitis, fistula and intestinal bleeding was 14.6 %, 0 %,

Metachronous metastases in distant organs are 0.7 % and 4.8 %, respectively. In the chemotherapy

found in 50 % of patients who underwent surgery for group, these cases were 15.2 %, 1.2 %, 0 % and 3.5 %,

locally advanced CRC, and synchronous secondary respectively. There were no significant differences

lesions are noted in 25 % of patients [9]. between the two groups regarding intestinal com-

More than 40 years ago, the diagnosis of stage plications [15].

IV colorectal cancer, even in the presence of single Equally important in the treatment of patients

metastatic foci, served as a reason for patients to with CRC oligometastases is the question of simul-

refuse specialized treatment, and the median life taneous or phased removal of the primary focus and

expectancy was no more than 12.5 months [10]. secondary changes. Some surgeons believe that si-

However, advances in chemotherapy, surgical multaneous removal of the primary lesion and me-

techniques, and assistive surgery have significant- tastases allows to increase the proportion of radical

ly expanded treatment options and improved out- operations, contribute to a more guaranteed con-

comes. The division of metastatic lesions of dis- tinuous adjuvant chemotherapy. Others advocate

tant organs into oligo- and poly-metastases is of gradual removal, which in turn leads to a decrease in

great importance in achieving positive results in the postoperative complications and mortality [16–18].

treatment of colorectal cancer. Since 2020, oligome- In recent years, there have been more and more

tastases should be understood as the presence of works describing the algorithm of treatment of these

a secondary lesion in the amount from 1 to 5 in one patients, which includes preoperative CT followed

or more organs [11]. Analyzing the literature data, it by liver resection, adjuvant CT and resection of the

is possible to trace the paradigm shift in the treat- primary tumor, explaining this by the fact that the

ment of oligometastatic cancer. most common cause of death of these patients is

Considering that surgical interventions in patients precisely a focus in the liver, and not the primary

with metastatic colorectal cancer were performed focus [19].

only for vital indications and, as a rule, were limit- Studies were conducted in which FOLFOX and

ed only to the formation of unloading colostomies FOLFIRI schemes were compared with each other,

or bypass anastomoses, the main and only treat- the analysis of the study showed the same effec-

ment of these patients for a long time was pallia- tiveness. These regimens can be used both in the

tive chemotherapy. The five-year survival rate did first and in the second line of chemotherapy for the

not exceed 10 % [12]. In this connection, in recent treatment of mCRC. It is also worth noting that the

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Южно-Российский онкологический журнал 2024. Т. 5, № 4. С. 20-28

Калмыкова Э. О., Ищенко Р. В., Стукалова О. Ю., Филимонов Д. А. Улучшение отдаленных результатов лечения больных олигометастатическим

колоректальным раком путем применения комбинированного подхода

best survival rates were achieved in patients who despite all the variety of options that have appeared

received all three chemotherapy drugs, i. e. infusion in the treatment of these patients, there are no clear

of 5-FU in combination with irinotecan and oxaliplatin recommendations and algorithms for the treatment

in the first and second lines [20]. of patients with CRC oligometastases.

The addition of targeted drugs to chemotherapeu- The study purpose is to improve the treatment

tic treatment significantly increased the life expec- results of patients suffering from CRC with oligo-

tancy of patients with metastatic colon cancer up to metastatic lesion by determining the most effective

22–25 months [21, 22]. combination of treatment methods for this cohort

The combination of chemoembolization of the he- of patients.

patic artery with systemic treatment of patients with

unresectable liver metastases leads to an increase PATIENTS AND METHODS

in average survival [23, 24]. Taking into account the

results of a randomized study, the median survival A retrospective analysis of the medical histories

with systemic chemotherapy alone was 17.5, and in of 71 patients with synchronous and metachronous

combination with chemoembolization – 28.4 months, oligometastases of CRC, who were treated in the

and in 30 % of patients metastasis resectability was conditions of the department of antitumor drug ther-

achieved [25]. apy of the PHI "ССН "RZD-Medicine" from December

In addition to surgical methods, ablation ther- 2001 to March 2023, the total median follow-up was

apy [such as radiofrequency ablation (RFA), cryo- 38.2 ± 8.7 months.

surgery, or microwave ablation] can be used as There were 36 (50.7 %) male and 35 (49.3 %) fe-

potentially curative treatments for liver and lung male patients with a morphologically verified diag-

metastases. In several studies, the 5-year OS ranged nosis of colon cancer (Table 1). The study included

from 20–30 % in patients with progressive CRC who patients with initial stages II and III, due to the ap-

had undergone RFA [26, 27]. pearance of metachronous metastases.

Thus, metastatic CRC is one of the most common The main criterion for inclusion in the study was

causes of death in patients from cancer, however, the presence of no more than 5 secondary foci of

the presence of oligometastatic lesions is a posi- CRC in one or more organs.

tive prognostic factor. Advances in the treatment of Taking into account the retrospective design of

oligometastatic CRC are crucial for increasing life the study, the mutational status of the primary tumor

expectancy, therefore, treatment strategies for these was excluded from the list of studied indicators due

patients should be discussed by a multidisciplinary to the lack of data on a number of observations.

team of experts in this field, taking into account Depending on the treatment methods, the pa-

various oncological factors. It should be noted that tients are divided into 2 groups. The first group

Table 1. Characteristics of the studied patients

Parameter Patients’ count

Stage of the disease n (%)

II 16 (22.5 %)

III 15 (21.1 %)

IV 40 (56.4 %)

Grade of tumor differentiation

G1 21 (29.6 %)

G2 38 (53.5 %)

G3 12 (16.9 %)

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South Russian Journal of Cancer 2024. Vol. 5, No. 4. P. 20-28

Kalmykova E. O., Ishchenko R. V., Stukalova O. Yu., Filimonov D. A. Improvement of long-term treatment results in oligometastatic colorectal cancer patients by using

a combined approach

included 35 patients who, at the first stage of com- cases. The number of metastatic nodes in each pa-

plex treatment, underwent simultaneous removal of tient varied from 1 to 5 and averaged 3.7 ± 1.1 foci.

the primary tumor and metastatic foci followed by The average sum of the diameters of metastatic

chemotherapy. The second group includes clinical nodes in the largest dimension was 4.4 ± 0.9 cm.

data on 36 patients who underwent primary lesion A comparative analysis of the studied groups of pa-

removal at the first stage of complex treatment fol- tients revealed no statistically significant differences

lowed by drug antitumor therapy. Patients in this in gender, age, number of metastatic foci and the

group underwent surgery for urgent indications due prevalence of the tumor process.

to the threat of massive bleeding from the primary As a result of the analysis of the data obtained

tumor, as well as in conditions of developing intes- in the group of patients with simultaneous surgical

tinal obstruction. treatment, it was revealed that at the first stage of

The first group included clinical data on 35 pa- complex treatment, abdominal perineal extirpation of

tients with colorectal cancer with oligometastases, the rectum (APER) + liver resection was performed in

of which 15 (42.9 %) men and 20 (57.1 %) wom- 4 (11.4 %) cases, in 1 (2.8 %) case – APER + removal

en. The average age of the patients was 58 ± 3.4 of metastasis of the right iliac region, in 4 (11.4 %)

years. Primary colorectal carcinoma was located in cases – anterior rectal resection + lung resection +

the rectum – in 15 (42.8 %) patients, in the sigmoid liver resection, in 3 (8.6 %) cases – anterior rectal

colon – in 13 (37.1 %) patients, in the rectosigmoid resection + lung resection, anterior rectal resection

department – in 4 (11.4 %) patients and in the trans- + liver resection was performed in 5 (14.3 %) cases.

verse colon – in 2 (5.7 %) patients, in the caecum – in Sigmoid colon resection + liver resection + lung re-

1 (2.6 %) of the patient. section was performed in 2 (5.7 %) cases, sigmoid

The location of oligometastases in the liver was colon resection + lung resection – in 4 (11.4 %) cas-

diagnosed in 18 (45 %) cases, lungs were detected es, sigmoid colon resection + ovarian resection – in

in 7 (13.8 %) cases, simultaneous lung and liver dam- 1 (2.8 %) case, sigmoid colon resection + liver resec-

age – in 6 (11.6 %) cases, damage to the right iliac tion – in 2 (5.7 %) cases. Hartmann type surgery +

region – in 1 (2 %) case, metastasis of the anterior anterior abdominal wall metastasectomy was per-

abdominal wall – in 1 (2 % in the ovary – in 2 (11.6 %) formed in 1 (2.8 %) cases, in 5 (14.3 %) cases, Hart-

cases. The number of metastatic nodes in each pa- mann type surgery + liver resection was performed.

tient varied from 1 to 5 and averaged 3.4 ± 1.2 foci. Surgical intervention in the volume of right–sided

The average sum of the diameters of metastatic hemicolectomy + liver resection was performed in

nodes in the largest dimension was 4.1 ± 1.2 cm. 1 (2.8 %) case, right- sided hemicolectomy + ovarian

In the second group, clinical data included 36 pa- resection – in 1 (2.8 %) case. Left-sided hemicolecto-

tients with colorectal cancer with oligometastatic my + liver resection was performed in 1 (2.8 %) case.

lesion, of whom 15 were women and 21 were men. At the second stage of complex treatment, the

The average age of the patients was 59.3 ± 2.1 years. patient of the first group underwent systemic che-

The primary tumor was located in the rectum – motherapy according to the following regimens: XE-

in 15 (41.2 %) patients, in the sigmoid colon – in LOX – in 13 (37.1 %) cases, FOLFOX-6 – in 11 (31.4 %)

10 (33.3 %) patients, in the rectosigmoid section – cases, XELIRI – in 3 (8.6 %) cases, capecitabine in

in 5 (9.8 %) patients and in the transverse colon – in monorode – in 5 (14.3 %) cases, Mayo – in 2 (5.7 %)

4 (13.7 %) patients, in the caecum – in 2 (2 %) of the cases, FOLFIRI – in 1 (2.8 %) case.

patient. In the group of surgical treatment of the primary

The location of oligometastases in the liver was focus followed by chemotherapy at the first stage of

diagnosed in 16 (45 %) cases, lungs were detected in complex treatment, APER was performed in 6 (16.7 %)

9 (13.8 %) cases, simultaneous damage to the lungs cases, anterior rectal resection in 13 (36.1 %) cases,

and liver – in 8 (11.6 %) cases, simultaneous damage Hartmann–type surgery in 5 (13.9 %) cases, sigmoid

to the ovary and rectovaginal septum – in 1 (2 %) colon resection in 6 (16.7 %) cases, in 2 (5.5 %) cas-

case, in the lymph node of the left axillary region – in es – resection of the transverse colon, in 3 (8.3 %)

1 (2 %) of cases, simultaneous lesion of the inguinal cases – right-s ided hemicolectomy, in 1  (2.8 %)

l/a on the left, adrenal gland and lungs – in 1 (2 %) of case – left-sided hemicolectomy.

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Калмыкова Э. О., Ищенко Р. В., Стукалова О. Ю., Филимонов Д. А. Улучшение отдаленных результатов лечения больных олигометастатическим

колоректальным раком путем применения комбинированного подхода

At the second stage of complex treatment, the tases was 63 ± 3.9 months, in the group of primary

patient of the second group underwent systemic tumor removal – 58 ± 3.8 months, p > 0.05 (Fig. 1).

chemotherapy according to the following regi- High CEA, the presence of stage IIIC (at the time

mens: XELOX – in 12 (33.3 %) cases, FOLFOX-6 – of diagnosis), and group (simultaneous removal of

in 10 (27.8 %) cases, XELIRI – in 2 (5.5 %) cases, the primary tumor and metastatic foci followed by

capecitabine in mono-mode – in 3 (8.3 %) cases, chemotherapy or removal of the primary tumor + CT)

Mayo – in 5 (13.9 %) cases, FOLFIRI – 3 (8.3 %) cas- were independent predictors affecting survival in the

es, irinotecan in mono mode – in 1 (2.8 %) case. Cox regression model (Table 2).

STUDY RESULTS DISCUSSION

As a result of an objective assessment of the ef- Despite significant progress in modern oncology,

fectiveness of the treatment based on a compre- surgical management remains the main method of

hensive examination, it was revealed in the group treating patients with oligometastases of colorectal

of simultaneous surgical treatment of patients that cancer. The most favorable option for synchronous

the response was achieved in 19 (54.3 %) cases, metastases is simultaneous surgery, i. e. simulta-

progression was diagnosed in 16 (45.7 %) cases. The neous removal of the primary focus and oligome-

median disease-free survival was 17.8 ± 6.3 months. tastases. Patyutko Yu. I. et al. conducted a study in

In the primary tumor removal group, the response which they compared the results of simultaneous

was received in 3 (8.3 %) cases, stabilization was removal of the primary tumor and oligometasta-

achieved in 14 (38.9 %) cases, and progression of ses, and sequential removals. The 3-year and 5-year

the tumor process was detected in 19 (52.8 %) cas- survival rates for simultaneous operations were

es. The median disease-free survival was 9.2 ± 3.2 48 % and 35 %, with phased operations – 55 % and

months. 38 % [28].

One-year, two- and three-year survival rates in the When oligometastases are localized in the lungs,

group of simultaneous removal of the primary tumor simultaneous interventions are preferred in the

and oligometastases and in the group of primary tu- choice of surgical tactics [29].

mor removal were 97.1 %, 88.6 %, 77.1 % and 100 %, Systemic treatment of patients with CRC oli-

80.5 %, 72.2 %, respectively. gometastases includes chemotherapy based on

The overall survival rate in the group of simultane- fluoropyrimidines, oxaliplatin, irinotecan, as well

ous removal of the primary tumor and oligometas- as treatment with targeted drugs. Combined

fluorouracil-b ased schemes with oxaliplatin (FOLF-

100 OX, XELOX, FLOX) or irinotecan (FOLFIRI, XELIRI)

are used as the 1st line in unresectable metastatic

CRC [30], as well as a triple combination of oxalipla-

75

tin, fluoropyrimidines, calcium folinate and irinote-

can (FOLFOXIRI).

50 In the presented clinical study, a comparative as-

sessment of the effectiveness of the treatment of

patients with colorectal cancer with oligometastases

25 was carried out, depending on the option of an inte-

0 grated approach. The results obtained turned out to

0 25 50 75 100 be multidirectional – the response to treatment and

Time progression were obtained in 54.3 % and 45.7 % of

 Group 1  Group 2 cases in the group of simultaneous removal of the

primary tumor and oligometastases versus 47.2 %

Fig. 1. Overall survival of patients of both groups (1 – group and 52.8 % of cases in the group of removal of the

of simultaneous surgical removal of the primary focus and primary tumor without oligometastases, respectively.

oligometastases, 2 – group of surgical removal of the primary focus The median recurrence-free survival was shorter in

followed by chemotherapy)

25

Survival (%)

South Russian Journal of Cancer 2024. Vol. 5, No. 4. P. 20-28

Kalmykova E. O., Ishchenko R. V., Stukalova O. Yu., Filimonov D. A. Improvement of long-term treatment results in oligometastatic colorectal cancer patients by using

a combined approach

the group of primary tumor removal without metas- CONCLUSION

tases (Table 2). The total annual survival of patients

was achieved by 100 % in the group of primary tu- In recent years, significant changes have occurred in

mor removal without metastases, compared with the treatment of patients with CRC oligometastases. It

97.1 % in the group of simultaneous surgical treat- should be noted that the final management tactics for

ment. Such a result is associated with a high risk of these patients has not been determined even today.

mortality during the first year against the background The choice of treatment tactics depends primarily on

of postoperative complications during extensive the localization and prevalence of the tumor process,

surgical interventions in the group of simultaneous the number of metastases and the organs affected by

removal of the primary tumor and oligometastases. them, and therefore the approach to the treatment of

The three-year survival rate is higher in the group patients with CRC oligometastases should be individ-

of simultaneous surgical treatment – 77.1 % versus ual. Removal of oligometastases was associated with

72.2 % in the group of surgical removal of the pri- a slight increase in overall survival, although the differ-

mary tumor. ence did not reach statistical significance. High CEA,

Thus, when choosing the treatment of patients the presence of stage IIIC (at the time of diagnosis),

with oligometastatic CRC lesion, it is important to and group of chemotherapy (simultaneous removal of

correctly assess all the risks of complications and the primary tumor and metastatic foci followed by or

adopt the only treatment option for a particular pa- removal of the primary tumor + CT) were independent

tient, with the participation of oncologists, surgeons, predictors affecting survival in the Cox model. Further

radiologists and chemotherapists. research is needed to increase the sample size.

Table 2. Factors affecting patient survival (Cox regression model)

Predictors Coeff. CI p

Groups (main, control) 2.49 1.02 – 6.06 0.045

Max. metastasis diameter 1.24 1.01 – 1.51 0.040

The sum of metastases

diameters 1.03 0.96 – 1.11 0.417

Age 0.98 0.94 – 1.02 0.388

Stage IIA 1.88 0.18 – 19.11 0.595

Stage IIB 0.00 0.00 – Inf 0.998

Stage IIIB 0.30 0.02 – 4.10 0.364

Stage IIIC 13.81 1.13 – 168.96 0.040

Stage IIIА 4.54 0.18 – 115.29 0.359

Stage IIIВ 0.30 0.01 – 6.84 0.450

Stage IIВ 16.64 0.83 – 332.56 0.066

Stage IV 1.55 0.16 – 15.16 0.708

Stage IVa 0.00 0.00 – Inf 0.998

High APA 0.89 0.10 – 7.78 0.917

High CEA 2.75 1.13 – 6.67 0.025

High Са19-9 1.27 0.41 – 3.93 0.679

Number of observations 71

R2 Nagelkerke 0.493

26

Южно-Российский онкологический журнал 2024. Т. 5, № 4. С. 20-28

Калмыкова Э. О., Ищенко Р. В., Стукалова О. Ю., Филимонов Д. А. Улучшение отдаленных результатов лечения больных олигометастатическим

колоректальным раком путем применения комбинированного подхода

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global Cancer Statistics 2020: GLOBOCAN Es-

timates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021 May;71(3):209–249.

https://doi.org/10.3322/caac.21660

2. The state of cancer care for the Russian population in 2019. Ed. by A. D. Kaprin, V. V. Starinsky, A. O. Shakhzadova. Moscow:

P. A. Herzen MNIOI – Branch of the National Medical Research Radiological Center, 2020, 236 p. (In Russ.).

3. Acciuffi S, Meyer F, Bauschke A, Croner R, Settmacher U, Altendorf-Hofmann A. Solitary colorectal liver metastasis: over-

view of treatment strategies and role of prognostic factors. J Cancer Res Clin Oncol. 2022 Mar;148(3):657–665.

https://doi.org/10.1007/s00432-021-03880-4

4. Al Battal M, Kanaan C, Labaied N, Breuskin I, Leboulleux S, Soufan R, et al. Colon Cancer Metastasis Within a NIFTP: A Case Re-

port and Review of the Literature. Head Neck Pathol. 2020 Sep;14(3):833–836. https://doi.org/10.1007/s12105-019-01089-z

5. Miura T, Mitsunori Y, Takeuchi M, Wada Y, Ishihara S, Nakajima Y, et al. A Case of Synchronous Solitary Splenic Metastasis

of Sigmoid Colon Cancer Treated with Laparoscopic Resection. Gan To Kagaku Ryoho. 2022 Apr;49(4):441–443.

6. Gkikas A, Kakos C, Lampridis S, Godolphin PJ, Patrini D. Preoperative prognostic factors for 5-year survival following pul-

monary metastasectomy from colorectal cancer: a systematic review and meta-analysis. Eur J Cardiothorac Surg. 2023

Mar 1;63(3):ezad059. https://doi.org/10.1093/ejcts/ezad059

7. Xu J, He Y, Cai Y, Huang Y, He Y. Isolated splenic metastases from rectal carcinoma 5 years after surgery: Case report.

Medicine (Baltimore). 2023 Jan 13;102(2):e32493. https://doi.org/10.1097/MD.0000000000032493

8. Chen L, Wang D, Mao W, Huang X, He C. A Case of Long-term Survival after Curative Resection for Synchronous Solitary

Adrenal Metastasis from Rectal Cancer. Pak J Med Sci. 2014 Jan;30(1):216–219. https://doi.org/10.12669/pjms.301.4341

9. Van der Geest LGM, Lam-Boer J, Koopman M, Verhoef C, Elferink MAG, de Wilt JHW. Nationwide trends in incidence, treatment

and survival of colorectal cancer patients with synchronous metastases. Clin Exp Metastasis. 2015 Jun;32(5):457–465.

https://doi.org/10.1007/s10585-015-9719-0

10. Steele G. Natural History Studies and the Evolution of Regional Treatment Modalities for Patients With Isolated Liver Metastases

From Primary Colon and Rectum Carcinoma. Cancer Control. 1996 Jan;3(1):34–41. https://doi.org/10.1177/107327489600300104

11. Lievens Y, Guckenberger M, Gomez D, Hoyer M, Iyengar P, Kindts I, et al. Defining oligometastatic disease from a radiation

oncology perspective: An ESTRO-ASTRO consensus document. Radiother Oncol. 2020 Jul;148:157–166.

https://doi.org/10.1016/j.radonc.2020.04.003

12. Kuipers EJ, Grady WM, Lieberman D, Seufferlein T, Sung JJ, Boelens PG, et al. Colorectal cancer. Nat Rev Dis Primers. 2015

Nov 5;1:15065. https://doi.org/10.1038/nrdp.2015.65

13. Norén A, Eriksson HG, Olsson LI. Selection for surgery and survival of synchronous colorectal liver metastases; a nation-

wide study. Eur J Cancer. 2016 Jan;53:105–114. https://doi.org/10.1016/j.ejca.2015.10.055

14. Karoui M, Roudot-Thoraval F, Mesli F, Mitry E, Aparicio T, Des Guetz G, et al. Primary colectomy in patients with stage IV

colon cancer and unresectable distant metastases improves overall survival: results of a multicentric study. Dis Colon

Rectum. 2011 Aug;54(8):930–938. https://doi.org/10.1097/DCR.0b013e31821cced0

15. Seo GJ, Park JW, Yoo SB, Kim SY, Choi HS, Chang HJ, et al. Intestinal complications after palliative treatment for asymp-

tomatic patients with unresectable stage IV colorectal cancer. J Surg Oncol. 2010 Jul 1;102(1):94–99.

https://doi.org/10.1002/jso.21577

16. Zeyara A, Torén W, Søreide K, Andersson R. The liver-first approach for synchronous colorectal liver metastases: A system-

atic review and meta-analysis of completion rates and effects on survival. Scand J Surg. 2022;111(1):14574969211030131.

https://doi.org/10.1177/14574969211030131

17. Wang SH, Song L, Tang JY, Sun WP, Li Z. Safety and long-term prognosis of simultaneous versus staged resection in

synchronous colorectal cancer with liver metastasis: a systematic review and meta-analysis. Eur J Med Res. 2022 Dec

19;27(1):297. https://doi.org/10.1186/s40001-022-00937-z

18. Hopt UT, Drognitz O, Neeff H. Timing of resection in patients with colorectal carcinoma and synchronous liver metastases.

Zentralbl Chir. 2009 Sep;134(5):425–429. https://doi.org/10.1055/s-0029-1224612

19. Mentha G, Majno PE, Andres A, Rubbia-Brandt L, Morel P, Roth AD. Neoadjuvant chemotherapy and resection of advanced

synchronous liver metastases before treatment of the colorectal primary. Br J Surg. 2006 Jul;93(7):872–878.

https://doi.org/10.1002/bjs.5346

27

South Russian Journal of Cancer 2024. Vol. 5, No. 4. P. 20-28

Kalmykova E. O., Ishchenko R. V., Stukalova O. Yu., Filimonov D. A. Improvement of long-term treatment results in oligometastatic colorectal cancer patients by using

a combined approach

20. Méndez Romero A, de Man RA. Stereotactic body radiation therapy for primary and metastatic liver tumors: From techno-

logical evolution to improved patient care. Best Pract Res Clin Gastroenterol. 2016 Aug;30(4):603–616.

https://doi.org/10.1016/j.bpg.2016.06.003

21. Folprecht G, Martinelli E, Mazard T, Modest DP, Tsuji A, Esser R, et al. Triplet chemotherapy in combination with anti-EGFR

agents for the treatment of metastatic colorectal cancer: Current evidence, advances, and future perspectives. Cancer

Treat Rev. 2022 Jan;102:102301. https://doi.org/10.1016/j.ctrv.2021.102301

22. Symonds LK, Cohen SA. Use of perioperative chemotherapy in colorectal cancer metastatic to the liver. Gastroenterol Rep

(Oxf). 2019 Oct;7(5):301–311. https://doi.org/10.1093/gastro/goz035

23. Stukalova OYu, Polikarpov AA, Isсhenko RV. Chemoembolization of the hepatic artery in the treatment of patients with che-

moresistant metastases of colorectal cancer. Review. Surgical practice. 2021;(3):61–68. (In Russ.).

https://doi.org/10.38181/2223-2427-2021-3-61-68, EDN: UIXOVJ

24. Karanicolas P, Beecroft JR, Cosby R, David E, Kalyvas M, Kennedy E, et al. Regional Therapies for Colorectal Liver Metasta-

ses: Systematic Review and Clinical Practice Guideline. Clin Colorectal Cancer. 2021 Mar;20(1):20–28.

https://doi.org/10.1016/j.clcc.2020.09.008

25. Yu Q, Zhang L, Fan S, Huang L, Wang X, Xindun C. The significance of transarterial chemoembolization combined with

systemic chemotherapy for patients with KRAS wild-type unresectable metachronous colorectal carcinoma with liver me-

tastases. J Cancer Res Ther. 2016 Dec;12(Supplement):C205–C211. https://doi.org/10.4103/0973-1482.200603

26. Lin YM, Paolucci I, Brock KK, Odisio BC. Image-Guided Ablation for Colorectal Liver Metastasis: Principles, Current Evi-

dence, and the Path Forward. Cancers (Basel). 2021 Aug 4;13(16):3926. https://doi.org/10.3390/cancers13163926

27. Matsui Y, Tomita K, Uka M, Umakoshi N, Kawabata T, Munetomo K, et al. Up-to-date evidence on image-guided thermal

ablation for metastatic lung tumors: a review. Jpn J Radiol. 2022 Oct;40(10):1024–1034.

https://doi.org/10.1007/s11604-022-01302-0

28. Patyutko YuI, Chuchuev ES, Podluzhny DV, Polyakov AN, Agafonova MG. Surgical tactics in the treatment of patients with

colorectal cancer with synchronous liver metastases. Oncological Coloproctology. 2011;2:13–19. (In Russ.).

29. Ryabov AB, Pikin OV, Kolbanov KI, Glushko VA, Vursol DA, Aleksandrov OA. Current approaches to treating patients with col-

orectal lung metastases. P. A. Herzen Journal of Oncology. 2018;7(6):52–59. https://doi.org/10.17116/onkolog2018705152,

EDN: YVRHLN

30. Sadot E, Groot Koerkamp B, Leal JN, Shia J, Gonen M, Allen PJ, et al. Resection margin and survival in 2368 patients un-

dergoing hepatic resection for metastatic colorectal cancer: surgical technique or biologic surrogate? Ann Surg. 2015

Sep;262(3):476–485. https://doi.org/10.1097/SLA.0000000000001427

Information about authors:

Elmira O. Kalmykova  – MD, oncologist, Department of Antitumor Drug Therapy, Lomonosov Moscow State University, Moscow, Russian Federation

ORCID: https://orcid.org/0009-0008-5842-1250

Roman V. Ishchenko – Dr. Sci. (Med.), director, V. K. Gusak institute of emergency and reconstructive surgery, Donetsk, Russian Federation; professor

at the Department of Surgical Diseases, Faculty of Fundamental Medicine of Lomonosov Moscow State University, Moscow, Russian Federation

ORCID: https://orcid.org/0000-0003-0260-6922, SPIN: 9021-7370, AuthorID: 1045336

Oksana Yu. Stukalova – MD, coloproctologist, oncologist, ALLORO Medical Center, Fryazino, Russian Federation

ORCID: https://orcid.org/0000-0003-3748-4750, SPIN: 4109-2387, AuthorID: 934990

Dmitry A. Filimonov – Dr. Sci. (Med.), Deputy Director for Scientific Work, V. K. Gusak institute of emergency and reconstructive surgery, Donetsk,

Russian Federation

ORCID: https://orcid.org/0000-0002-4542-6860, SPIN: 1491-8262, AuthorID: 786590, Scopus Author ID: 58385159700

Contribution of the authors:

Kalmykova E. O. – concept and design of the study, collection and processing of material, statistical data processing, writing the text;

Ishchenko R. V. – scientific guidance, editing, approval of the final version of the article;

Stukalova O. Yu. – concept and design of the study, editing;

Filimonov D. A. – concept and design of the study, editing, revision of the text.

28