World J Oncol

World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access

Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc

Journal website https://www.wjon.org

Original Article

Volume 15, Number 2, April 2024, pages 298-308

Gene Expression Profile-Guided Personalized Intraperitoneal Chemotherapy for Gastric Cancer Peritoneal Carcinomatosis

Figure 1. Algorithm for personalized chemotherapy depending on the chemotherapy genes expression at different sites: stomach tumors, peritoneal metastases, lymph node metastases and hematogenous metastases (if any).

Figure 2. Progression-free survival according to the Kaplan-Meier method in groups with personalized prescription of chemotherapy (basic group) and control. Log rank P = 5.8 × 10^-16 (Chi-square = 65.5) (statistically significant survival rate is confirmed).

Figure 3. Overall survival according to the Kaplan-Meier method in groups with personalized prescription of chemotherapy (basic group) and control. Log rank P = 1.3 × 10^-17 (Chi-square = 72.9) (statistically significant survival rate is confirmed).

Figure 4. Overall survival of patients with gastric cancer with synchronous peritoneal carcinomatosis, depending on the volume of cytoreduction R in the control group (a) and in the basic group (b). (a) Log rank P = 0.347, Chi-square = 2.11. (b) Log rank P = 0.426, Chi-square = 1.71.

Figure 5. Overall survival of patients with gastric cancer with synchronous peritoneal carcinomatosis depending on the lymphadenectomy D volume in the control group (a) and in the basic group (b). (a) Log rank P = 0.189, Chi-square = 1.73. (b) Log rank (D1/D2) P = 0.025, Chi-square = 7.35.

**Table 1.** inclusion and Exclusion Criteria
Inclusion criteria	Exclusion criteria
HER2: human epidermal growth factor receptor 2; ECOG: Eastern Cooperative Oncology Group; WHO: World Health Organization; PCI: Peritoneal Carcinomatosis Index; CEC: cardioesophageal cancer.
Age from 18 to 68 years	Age over 68 years
Histologically verified gastric and cardioesophageal cancer (Sievert III) with signs of dissemination (carcinomatosis, ascites, metastatic ovarian involvement) subject to cytoreductive surgery.	Patients with cardioesophageal cancer with lesions of the esophagus above 4 cm, requiring esophageal extirpation (CEC, Sievert I - II)
HER2/neu status: negative	Patients with gastric cancer stage I - IIIC (T1-4 N0-3 M0)
PCI is from 1 to 12	HER2/neu status: positive
ECOG (WHO) is not more than two points, on the Karnofsky scale more than 70%	PCI is from 13 to 39
Consent of the patient to be included in the study	ECOG (WHO) is more than two points, on the Karnofsky scale less than 70%
	Multiple distant metastases (liver, lungs, bones, etc.)
	Obstructive jaundice (a consequence of the bile duct block, at the level of the junction of the liver/choledochus, metastasis - affected lymph nodes). True germination into the head and body of the pancreas. Impaired liver function and kidney function

Table 1. inclusion and Exclusion Criteria

Inclusion criteria

Exclusion criteria

HER2: human epidermal growth factor receptor 2; ECOG: Eastern Cooperative Oncology Group; WHO: World Health Organization; PCI: Peritoneal Carcinomatosis Index; CEC: cardioesophageal cancer.

Age from 18 to 68 years

Age over 68 years

Histologically verified gastric and cardioesophageal cancer (Sievert III) with signs of dissemination (carcinomatosis, ascites, metastatic ovarian involvement) subject to cytoreductive surgery.

Patients with cardioesophageal cancer with lesions of the esophagus above 4 cm, requiring esophageal extirpation (CEC, Sievert I - II)

HER2/neu status: negative

Patients with gastric cancer stage I - IIIC (T1-4 N0-3 M0)

PCI is from 1 to 12

HER2/neu status: positive

ECOG (WHO) is not more than two points, on the Karnofsky scale more than 70%

PCI is from 13 to 39

Consent of the patient to be included in the study

ECOG (WHO) is more than two points, on the Karnofsky scale less than 70%

Multiple distant metastases (liver, lungs, bones, etc.)

Obstructive jaundice (a consequence of the bile duct block, at the level of the junction of the liver/choledochus, metastasis - affected lymph nodes). True germination into the head and body of the pancreas. Impaired liver function and kidney function

**Table 2.** Five Chemotherapy Regimens Developed
PC: peritoneal carcinomatosis; 5-FU: 5-fluorouracil.
1	PC	Paclitaxel 135 mg/m² on the first day, intravenously, drip for 3 h, cisplatin 50 mg on the second day, intraperitoneally with 200 mL of saline, paclitaxel 65 mg/m² on the eighth day, intraperitoneally with 200 mL of saline. Interval: 21 days.
2	GemCap + С (intraperitoneally)	Gemzar 800 mg/m², intravenously on the first and eighth days; cisplatin 50 mg intraperitoneally per 200 mL of saline on the fourth day; capecitabine 1,500 mg/m² for 14 days. Interval: 21 days.
3	TPFL (modification DCF) with intraperitoneal insertion of cisplatin	Docetaxel 75 mg/m² intravenously over 1 h on the second day; cisplatin 50 mg intravenously, 1 h on the second day; cisplatin 50 mg intraperitoneally per 200 mL saline on the third day; 5-FU 500 mg/m² 3-h infusion on the 1 - 3 days; leucovorin 50 mg intravenously, on the 1 - 3 days before 5-FU insertion. Interval: 21 days.
4	FOLFIRI + С (intraperitoneally)	Irinotecan 170 mg/m² intravenously, infusion 90 min; leucovorin 400 mg/m² intravenously, infusion 2 h on the first day; 5-FU 400 mg/m² intravenously, then 2,400 mg/m² intravenously, infusion 46 h. Cisplatin 50 mg intraperitoneally per 200 mL of saline on the second day. Interval: 21 days.
5	XELIRI + C (intraperitoneally)	Irinotecan 230 mg/m² intravenously, infusion 60 - 90 min, on the first day; cisplatin 50 mg intraperitoneally per 200 mL saline, on the second day; capecitabine 1,800 mg/m² daily for 14 days. Interval: 21 days.

Table 2. Five Chemotherapy Regimens Developed

PC: peritoneal carcinomatosis; 5-FU: 5-fluorouracil.

Paclitaxel 135 mg/m² on the first day, intravenously, drip for 3 h, cisplatin 50 mg on the second day, intraperitoneally with 200 mL of saline, paclitaxel 65 mg/m² on the eighth day, intraperitoneally with 200 mL of saline. Interval: 21 days.

GemCap + С (intraperitoneally)

Gemzar 800 mg/m², intravenously on the first and eighth days; cisplatin 50 mg intraperitoneally per 200 mL of saline on the fourth day; capecitabine 1,500 mg/m² for 14 days. Interval: 21 days.

TPFL (modification DCF) with intraperitoneal insertion of cisplatin

Docetaxel 75 mg/m² intravenously over 1 h on the second day; cisplatin 50 mg intravenously, 1 h on the second day; cisplatin 50 mg intraperitoneally per 200 mL saline on the third day; 5-FU 500 mg/m² 3-h infusion on the 1 - 3 days; leucovorin 50 mg intravenously, on the 1 - 3 days before 5-FU insertion. Interval: 21 days.

FOLFIRI + С (intraperitoneally)

Irinotecan 170 mg/m² intravenously, infusion 90 min; leucovorin 400 mg/m² intravenously, infusion 2 h on the first day; 5-FU 400 mg/m² intravenously, then 2,400 mg/m² intravenously, infusion 46 h. Cisplatin 50 mg intraperitoneally per 200 mL of saline on the second day. Interval: 21 days.

XELIRI + C (intraperitoneally)

Irinotecan 230 mg/m² intravenously, infusion 60 - 90 min, on the first day; cisplatin 50 mg intraperitoneally per 200 mL saline, on the second day; capecitabine 1,800 mg/m² daily for 14 days. Interval: 21 days.

**Table 3.** Clinical and Pathological Characteristics of Patients With Gastric Cancer With Synchronous Peritoneal Carcinomatosis
Characteristics	Basic group (n = 35)	Control group (n = 35)	P value (Mann-Whitney U-test or χ² Pearson test)
Age, mean (Q25, Q75) years	57 (45, 63)	57.5 (43, 62)	U = 612.5/P = 0.99
Men, n (%)	18 (51%)	18 (51%)	χ² = 0,000000/P = 1
Women, n (%)	17 (49%)	17 (49%)
Histological subtype
Low-grade adenocarcinoma	20 (57%)	25 (71%)	P = 0.32
Cricoid cell carcinoma	15 (43%)	10 (29%)
The volume of the operational aid
Extended combined palliative gastrectomy according to Roux	16 (46%)	12 (34%)	P = 0.47
Palliative gastrectomy according to Roux	19 (54%)	23 (66%)
Postoperative complications
No complications	18 (51%)	14 (40%)	χ² = 9.960361/P = 0.13

Table 3. Clinical and Pathological Characteristics of Patients With Gastric Cancer With Synchronous Peritoneal Carcinomatosis

Characteristics

Basic group (n = 35)

Control group (n = 35)

P value (Mann-Whitney U-test or χ² Pearson test)

Age, mean (Q25, Q75) years

57 (45, 63)

57.5 (43, 62)

U = 612.5/P = 0.99

Men, n (%)

18 (51%)

χ² = 0,000000/P = 1

Women, n (%)

17 (49%)

Histological subtype

Low-grade adenocarcinoma

20 (57%)

25 (71%)

P = 0.32

Cricoid cell carcinoma

15 (43%)

10 (29%)

The volume of the operational aid

Extended combined palliative gastrectomy according to Roux

16 (46%)

12 (34%)

P = 0.47

Palliative gastrectomy according to Roux

19 (54%)

23 (66%)

Postoperative complications

No complications

18 (51%)

14 (40%)

χ² = 9.960361/P = 0.13

**Table 4.** The Main Criteria for the Effectiveness of Cytoreductive Surgery in Patients With Gastric Cancer, With Synchronous Peritoneal Carcinomatosis
Variables	Basic group (n = 35)	Control group (n = 35)	P value (Mann-Whitney U-test or χ² Pearson test)
PCI: Peritoneal Carcinomatosis Index; CC: completeness of cytoreduction.
R: resection boundary
R0	24 (69%)	9 (26%)	χ² = 13.39/P = 0.0012
R1	1 (3%)	5 (14%)
R2	10 (29%)	21 (60%)
D: volume of lymph node dissection
D1+	11 (31%)	25 (71%)	χ² = 11.94/P = 0.003
D2	24 (69%)	10 (29%)
PCI: (PCI from English: Peritoneal Cancer Index)
PCI (0 - 4)	10 (29%)	5 (14%)	χ² = 2.12/P = 0.3465
PCI (5 - 8)	11 (31%)	13 (37%)
PCI (9 - 12)	14 (40%)	17 (49%)
CC score: scale for assessing the completeness of cytoreduction
CC-0 score	24 (69%)	13 (37%)	χ² = 7.97/P = 0.0466
CC-1 score	6 (17%)	9 (26%)
CC-2 score	2 (6%)	8 (23%)
CC-3 score	3 (8%)	5 (14%)

Table 4. The Main Criteria for the Effectiveness of Cytoreductive Surgery in Patients With Gastric Cancer, With Synchronous Peritoneal Carcinomatosis

Variables

Basic group (n = 35)

Control group (n = 35)

P value (Mann-Whitney U-test or χ² Pearson test)

PCI: Peritoneal Carcinomatosis Index; CC: completeness of cytoreduction.

R: resection boundary

24 (69%)

9 (26%)

χ² = 13.39/P = 0.0012

1 (3%)

5 (14%)

10 (29%)

21 (60%)

D: volume of lymph node dissection

D1+

11 (31%)

25 (71%)

χ² = 11.94/P = 0.003

24 (69%)

10 (29%)

PCI: (PCI from English: Peritoneal Cancer Index)

PCI (0 - 4)

10 (29%)

5 (14%)

χ² = 2.12/P = 0.3465

PCI (5 - 8)

11 (31%)

13 (37%)

PCI (9 - 12)

14 (40%)

17 (49%)

CC score: scale for assessing the completeness of cytoreduction

CC-0 score

24 (69%)

13 (37%)

χ² = 7.97/P = 0.0466

CC-1 score

6 (17%)

9 (26%)

CC-2 score

2 (6%)

8 (23%)

CC-3 score

3 (8%)

5 (14%)