Innovations and challenges in intraperitoneal chemotherapy for peritoneal metastatic carcinoma

doi:10.19401/j.cnki.1007-3639.2024.09.003

Abstract

Abstract:

Peritoneal metastatic carcinoma refers to the spread of malignant tumors from the primary site to the peritoneum. It is commonly observed in the advanced stages of various cancer types, including gastric cancer, colorectal cancer, ovarian cancer and pseudomyxoma peritonei (PMP). Peritoneal metastatic carcinoma seriously impair human health due to their high recurrence and mortality rates, and palliative treatment based on chemotherapy is usually provided after radical surgery or in the advanced stage of peritoneal metastases. The difficulties in the treatment of peritoneal metastatic carcinoma are the lack of targeted drugs and the difficulty of drugs to cross the blood-peritoneal barrier, resulting in poor systemic effects. Intraperitoneal chemotherapy, as an important therapeutic means, has a broad application prospect in the treatment of peritoneal metastatic carcinoma. In recent years, innovations in intraperitoneal chemotherapy techniques such as hyperthermic intraperitoneal chemotherapy (HIPEC), pressurized intraperitoneal aerosol chemotherapy (PIPAC) and the development of novel drugs have significantly improved patients' quality of life. The development of novel drugs has significantly improved patient survival. However, the diversity and complexity of these diseases have led to clinical variability and uncertainty in the efficacy of intraperitoneal chemotherapy in terms of treatment strategies such as mode of administration, drug type and dose. Although evidence-based guidelines and recommended treatment strategies have been developed, there is a need to further support these regimens through additional clinical trials and higher levels of evidence-based medicine. This review summarized the development history and recent advances in intraperitoneal chemotherapy, compared and analyzed the treatments such as surgery combined with traditional IPC, HIPEC and PIPAC, and summarized the research progress of recently conducted intraperitoneal chemotherapy techniques; moreover, in terms of the clinical application of intraperitoneal chemotherapy techniques, this paper elaborated on its use in diseases such as gastric cancer, colorectal cancer, gynecological oncology, PMP, cholangiocarcinoma and pancreatic cancer. For the limitations of intraperitoneal chemotherapy technology, it is proposed that the innovative development of nanomedicine is expected to provide a safer and more effective option for the treatment of peritoneal metastatic carcinoma. In conclusion, this review summarized the latest progress, shortcomings and future development of intraperitoneal chemotherapy, with the aim of providing a feasible direction for more effective clinical treatment of peritoneal metastatic carcinoma.

Key words: Peritoneal metastatic carcinoma, Intraperitoneal chemotherapy, Hyperthermic intraperitoneal chemotherapy, Pressurized intraperitoneal aerosol chemotherapy, Nano-drug, Targeted therapy

CLC Number:

R730.53

FENG Xinying, WANG Bing, LIU Peifeng. Innovations and challenges in intraperitoneal chemotherapy for peritoneal metastatic carcinoma[J]. China Oncology, 2024, 34(9): 827-837.

Figures/Tables 4

Fig. 1

Fig. 2

Tab. 1

Commonly used IPC protocols in clinical practice"

Preoperative diagnosis	Surgical program	Research type	Number of sample		Chemotherapy protocol		Result	Reference
Preoperative diagnosis	Surgical program	Research type	Trial	Control	Trial	Control	Result	Reference
Gastric cancer +Peritoneal cancer	CRS	Gastripec-Ⅰ	52	53	CRS+HIPEC (mitomycin 15 mg/m²+cisplatin 75 mg/m², 42 ℃, 60 min)	Simple CRS; 11 cases of postoperative chemotherapy (such as fluorouracil)	Better PFS and MFS	[27]
Gastric cancer (c>T3)	Radical gastrectomy for gastric cancer+D2 lymphnode dissection	Phase Ⅲ clinical trial	40	40	CRS+HIPEC [cisplatin 50 mg/m², 60 min, (42.0±1.0) ℃]; 22 cases within 1 month after surgery XELOX regimen with 6 standard doses	XELOX regimen with 6 standard doses within 1 month after surgery	Low DFS and peritoneal recurrence	[42]
Colon cancer (T4N0-2M0)	CRS	Phase Ⅲ clinical trial	89	95	CRS+HIPEC (mitomycin 30 mg/m² ); Receive routine adjuvant systemic chemotherapy combined with oxaliplatin and capecitabine within 12 weeks after surgery	CRS+systemic chemotherapy combined with oxaliplatin and capecitabine within 12 weeks	Improve 3 years LC rate	[43]
Colon cancer (T4N0-2M0)	CRS	Phase Ⅲ clinical trial	100	102	HIPEC after surgery 5-8 weeks (oxaliplatin 460 mg/m², 30 min)+ chemotherapy with intravenous fluorouracil/calcium folinate	Hydrostatic injection of fluorouracil/calcium folinate adjuvant chemotherapy	No significant difference	[44]
Appendix/colorectal cancer+peritoneal cancer		Phase Ⅰ clinical trial	12		PIPAC (oxaliplatin 90 mg/m² )+whole body chemotherapy (fluorouracil+calcium folinate)		Safe and feasible	[36]
Phase Ⅲ/Ⅳ ovarian cancer	CRS	Phase Ⅲ clinical trial	92	92	CRS+HIPEC (cisplatin 75 mg/m², 90 min, 41.5 ℃); 6 cycles of adjuvant chemotherapy (paclitaxel 175 mg/m²+ carboplatin 5 mg/mL)	6 cycles of adjuvant chemotherapy (paclitaxel 175 mg/m² +carboplatin 5 mg/mL)	Cannot improve PFS and OS	[45]
Ovarian cancer	CRS	Clinical research	100		PIPAC (cisplatin 7.5 mg/m²+ doxorubicin 1.5 mg/m²)		The result is meaningless	[46]
Breast cancer/endometrial cancer+peritoneal cancer	Hysterectom/mastectomy	Cohort study	44		PIPAC (cisplatin 7.5 mg/m² +doxorubicin 1.5 mg/m²); Later changed to PIPAC (cisplatin 10.5 mg/m²+doxorubicin 2.1 mg/m²)		Improve survival rate and histological regression	[47]
Mucinous carcinoma of the appendix +PMP	CRS+Peritoneal resection surgery	Case report	1		CRS+HIPEC (mitomycin 35 mg/m², 42 ℃, 90 min)		Improve survival rate	[48]
Appendiceal tumor +PMP	CRS+Peritoneal resection surgery	Case report	1		CRS+IPC (cisplatin 30 mg/m²+ docetaxel 30 mg/m²)+ HIPEC (oxaliplatin 4 300 mg+fluorouracil 500 mg, 42.5-43.5 ℃, 40 min)		Good postoperative recovery	[49]
Intrahepatic cholangiocarcinoma + peritoneal cancer	CRS	Cohort study	51	61	CRS+HIPEC (fluorouracil 1 000 mg/BSA+cisplatin 40 mg/m², 400-600 mL/min)+ IPC (fluorouracil or oxaliplatin)	Simple CRS +IPC (fluorouracil or oxaliplatin)	Improve OS and survival rate	[50]
Pancreatic cancer +peritoneal cancer	Pancreatic surgery or systemic chemotherapy	Prospective study	35		PIPAC (30 mL/min, cisplatin 7.5 mg/m²+ doxorubicin 1.5 mg/m², 92 min)		Improve survival rate and histological regression	[51]

Tab. 1

Tab. 2

Research on nanodrugs in IPC"

Carrier	Material	Load	Cell/animal model	Administration method	Indication	Advantage/result	Reference
Polymeric micelles	Polyethylene glycol, lactic acid hydroxy acetic acid copolymer	Oxaliplatin	Tumor bearing mouse model	IP, IV	Colorectal cancer with peritoneal metastasis	IP reduces the systemic distribution of drugs and the toxicity to major organs, improves the precision of treatment	[67]
Nano hydrogel	Carboxymethyl chitosan, polylactic acid hyperbranched polyglycerol	Paclitaxel, anti-PD-1 antibody	C57BL/6 mouse model	IP	Ovarian cancer with peritoneal metastasis	① Low system toxicity and good therapeutic effect; ② Good biocompatibility	[68]
¹⁴C-eNP	eNPs, ¹⁴C	Paclitaxel	Mesothelioma of peritoneum tumor bearing mouse model	IP, IV	Mesothelioma of peritoneum	IP efficiency is higher	[34]
Liposomes	Liposomes encoding firefly luciferase mRNA	mRNA	C57BL/6 mouse model	IP, IV	Pancreatic related cancer	IP enhances the ability of mRNA delivery to the pancreas	[69]
Liposomes	Cationic assisted lipids, liposomes encoding firefly luciferase mRNA	mRNA	C57BL/6 mouse model	IP, IV	Pancreatic related cancer	IP reduces off target delivery to the liver and spleen	[69]
Liposomes	Phosphatidylserine, β-sitosterol	mRNA	CT26-luc mouse model	IP		High transfection efficiency and selectivity	[70]
CAR-Ms		PD-1 antibody	CT26 mouse model	IP	Late stage diffuse peritoneal tumor	Activate adaptive immune response provide new strategies for solid tumor treatment	[70]
Liposomes	C12-200 cation, Cy5.5 dye	siRNA	Mouse model	IP		Enhancing the potential of using LPM to transport oligonucleotides encapsulated in nanoparticles for cancer treatment	[71]
Liposomes	4A3-SCC-10/PH	mRNA	tdTomato mouse model	IP	Liver cancer	Improving mRNA delivery efficiency in vivo has the potential to treat liver cancer	[71]
Nanoparticles	Silicon dioxide, polystyrene nanoparticles, polylactic acid hydroxyacetic acid copolymer		Mouse model	IP, IV	Ovarian cancer with abdominal metastasis	① IP has high targeting efficiency; ② Lay the foundation for the treatment of metastatic ovarian cancer	[72]
Nanoparticles	PEG^5k-BA4, PEG^5k-Cys4-L8-CA8	Paclitaxel, Betulinic acid	A2780/Adr cells, ovarian cancer mouse model	IP	Ovarian cancer	① Achieve precise drug release; ② Overcome multidrug resistance in ovarian cancer	[73]

Tab. 2

References 76

[1]	中国抗癌协会腹膜肿瘤专业委员会. 中国肿瘤整合诊治指南:腹膜肿瘤(胃肠肿瘤部分)[J]. 消化肿瘤杂志(电子版), 2023, 15(2): 100-108.
	Chinese Society of Peritoneal Oncology, China Anti-Cancer Association. China Anti-Cancer Association guidelines for holistic integrative management of cancer-peritoneal tumours from gastrointestinal tract[J]. J Digest Oncol (Elect Ver), 2023, 15(2): 100-108.
[2]	唐鸿生, 阮强, 崔书中. 《中国肿瘤整合诊治指南: 腹膜肿瘤》解读[J]. 消化肿瘤杂志(电子版), 2023, 15(2): 109-113.
	TANG H S, RUAN Q, CUI S Z. Interpretation of China Anti-Cancer Association (CACA) guidelines for holistic integrative management of cancer-peritoneal tumours[J]. J Digest Oncol (Elect Ver), 2023, 15(2): 109-113.
[3]	LEI Z Y, WANG J H, LI Z, et al. Hyperthermic intraperitoneal chemotherapy for gastric cancer with peritoneal metastasis: a multicenter propensity score-matched cohort study[J]. Chin J Cancer Res, 2020, 32(6): 794-803.
[4]	关天培, 雷子颖, 崔书中. 结肠直肠癌腹膜转移防治临床研究[J]. 外科理论与实践, 2021, 26(1): 7-10.
	GUAN T P, LEI Z Y, CUI S Z. Clinical study on prevention and treatment of peritoneal metastasis of colorectal cancer[J]. J Surg Concepts Pract, 2021, 26(1): 7-10.
[5]	樊代明, 崔书中. 中国肿瘤整合诊治指南:腹膜肿瘤(2022)[M]. 天津科学技术出版社, 2022.
	FAN D M, CUI S Z. Guidelines for integrated diagnosis and treatment of tumors in china: peritoneal tumors (2022)[M]. Tianjin Sci Technol Press, 2022.
[6]	HOSSAIN M B, HALDAR NEER A H. Chemotherapy[M]//QAZI A S, TARIQ K. Therapeutic approaches in cancer treatment: vol. 185. Berlin: Springer, 2023: 49-58.
[7]	JACQUET P, SUGARBAKER P H. Peritoneal-plasma barrier[M]//SUGARBAKER P H. Peritoneal carcinomatosis: principles of management. Berlin: Springer, 1996: 53-63.
[8]	SADEGHI B, ARVIEUX C, GLEHEN O, et al. Peritoneal carcinomatosis from non-gynecologic malignancies: results of the EVOCAPE 1 multicentric prospective study[J]. Cancer, 2000, 88(2): 358-363. doi: 10.1038/nrc.2016.108 pmid: 27834398
[9]	JAABACK K, JOHNSON N, LAWRIE T A. Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer[J]. Cochrane Database Syst Rev, 2016, 2016(1): CD005340.
[10]	CARLIER C, MATHYS A, JAEGHERE E D, et al. Tumour tissue transport after intraperitoneal anticancer drug delivery[J]. Int J Hyperthermia, 2017, 33(5): 534-542.
[11]	GUCHELAAR N A D, NASSERINEJAD K, MOSTERT B, et al. Intraperitoneal chemotherapy for peritoneal metastases of gastric origin: a systematic review and meta-analysis[J]. Br J Surg, 2024, 111(5): znae116.
[12]	SHI J J, KANTOFF P W, WOOSTER R, et al. Cancer nanomedicine: progress, challenges and opportunities[J]. Nat Rev Cancer, 2017, 17(1): 20-37.
[13]	AL-QUTEIMAT O M, AL-BADAINEH M A. Intraperitoneal chemotherapy: rationale, applications, and limitations[J]. J Oncol Pharm Pract, 2014, 20(5): 369-380.
[14]	FUJIMOTO S, SHRESTHA R D, KOKUBUN M, et al. Intraperitoneal hyperthermic perfusion combined with surgery effective for gastric cancer patients with peritoneal seeding[J]. Ann Surg, 1988, 208(1):36-41. doi: 10.1097/00000658-198807000-00005 pmid: 3133994
[15]	TEMPFER C B, SOLASS W, REYMOND M A. Pressurized intraperitoneal chemotherapy (PIPAC) in women with gynecologic malignancies: a review[J]. Wien Med Wochenschr, 2014, 164(23/24): 519-528.
[16]	SOLASS W, KERB R, MÜRDTER T, et al. Intraperitoneal chemotherapy of peritoneal carcinomatosis using pressurized aerosol as an alternative to liquid solution: first evidence for efficacy[J]. Ann Surg Oncol, 2014, 21(2): 553-559. doi: 10.1245/s10434-013-3213-1 pmid: 24006094
[17]	COCCOLINI F, COTTE E, GLEHEN O, et al. Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials[J]. Eur J Surg Oncol, 2014, 40(1): 12-26. doi: 10.1016/j.ejso.2013.10.019 pmid: 24290371
[18]	FILIS P, MAURI D, MARKOZANNES G, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) for the management of primary advanced and recurrent ovarian cancer: a systematic review and meta-analysis of randomized trials[J]. ESMO Open, 2022, 7(5): 100586.
[19]	CORTÉS-GUIRAL D, HÜBNER M, ALYAMI M, et al. Primary and metastatic peritoneal surface malignancies[J]. Nat Rev Dis Primers, 2021, 7(1): 91.
[20]	SANTULLO F, PACELLI F, ABATINI C, et al. Cytoreduction and hyperthermic intraperitoneal chemotherapy for pseudomyxoma peritonei of appendiceal origin: a single center experience[J]. Front Surg, 2021, 8: 715119.
[21]	KUSAMURA S, BARRETTA F, YONEMURA Y, et al. The role of hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei after cytoreductive surgery[J]. JAMA Surg, 2021, 156(3): e206363.
[22]	PAPANTONI E, NTATSIS K, KYZIRIDIS D, et al. Twenty-years’ experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for pseudomyxoma peritonei (PMP)[J]. J BUON, 2021, 26(4): 1647-1652.
[23]	MAJEED A, ALAPARTHI S, HALEGOUA-DEMARZIO D, et al. Complete pathologic response to gemcitabine and oxaliplatin chemotherapy after prior therapies in a patient with hepatocellular carcinoma and peritoneal metastases undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J]. World J Oncol, 2024, 15(3): 511-520. doi: 10.14740/wjon1840 pmid: 38751709
[24]	HUNG K C, YANG K L, HUANG G C, et al. Cytoreduction surgery and hyperthermic intraperitoneal chemotherapy for treating advanced peritoneal metastases of hepatocellular carcinoma[J]. Pleura Peritoneum, 2020, 5(2): 20190030.
[25]	HERNANDEZ D L, RESTREPO J, GARCIA MORA M. Peritoneal metastasis of cholangiocarcinoma treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy at the instituto nacional de cancerología, Colombia[J]. Cureus, 2020, 12(1): e6697.
[26]	FRASSINI S, CALABRETTO F, GRANIERI S, et al. Intraperitoneal chemotherapy in the management of pancreatic adenocarcinoma: a systematic review and meta-analysis[J]. Eur J Surg Oncol, 2022, 48(9): 1911-1921. doi: 10.1016/j.ejso.2022.05.030 pmid: 35688711
[27]	RAU B, LANG H, KOENIGSRAINER A, et al. Effect of hyperthermic intraperitoneal chemotherapy on cytoreductive surgery in gastric cancer with synchronous peritoneal metastases: the phase Ⅲ GASTRIPEC-I trial[J]. J Clin Oncol, 2024, 42(2): 146-156.
[28]	LIU G, JI Z H, YU Y, et al. Treatment of hypermyoglobinemia after CRS+HIPEC for patients with peritoneal carcinomatosis: a retrospective comparative study[J]. Medicine, 2017, 96(45): e8573.
[29]	BRANDL A, ZIELINSKI C B, RAUE W, et al. Peritoneal metastases of rare carcinomas treated with cytoreductive surgery and HIPEC-a single center case series[J]. Ann Med Surg, 2017, 22: 7-11.
[30]	GLEHEN O, MOHAMED F, GILLY F N. Peritoneal carcinomatosis from digestive tract cancer: new management by cytoreductive surgery and intraperitoneal chemohyperthermia[J]. Lancet Oncol, 2004, 5(4): 219-228. doi: 10.1016/S1470-2045(04)01425-1 pmid: 15050953
[31]	FRIEDRICH M, ZINN W, KOLNSBERG L, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) for ovarian cancer: evaluation of side effects in a single institution cohort[J]. Anticancer Res, 2020, 40(3): 1481-1486. doi: 10.21873/anticanres.14092 pmid: 32132047
[32]	ALYAMI M, HÜBNER M, GRASS F, et al. Pressurised intraperitoneal aerosol chemotherapy: rationale, evidence, and potential indications[J]. Lancet Oncol, 2019, 20(7): e368-e377.
[33]	GUEL-KLEIN S, ALBERTO VILCHEZ M E, CEELEN W, et al. Is PIPAC a treatment option in upper and lower gastrointestinal cancer with peritoneal metastasis?[J]. Visc Med, 2022, 38(2): 90-98.
[34]	COLBY A H, KIRSCH J, PATWA A N, et al. Radiolabeled biodistribution of expansile nanoparticles: intraperitoneal administration results in tumor specific accumulation[J]. ACS Nano, 2023, 17(3): 2212-2221. doi: 10.1021/acsnano.2c08451 pmid: 36701244
[35]	MOUKARZEL L A, FERRANDO L, DOPESO H, et al. Hyperthermic intraperitoneal chemotherapy (HIPEC) with carboplatin induces distinct transcriptomic changes in ovarian tumor and normal tissues[J]. Gynecol Oncol, 2022, 165(2): 239-247. doi: 10.1016/j.ygyno.2022.02.022 pmid: 35292180
[36]	RAOOF M, WHELAN R L, SULLIVAN K M, et al. Safety and efficacy of oxaliplatin pressurized intraperitoneal aerosolized chemotherapy (PIPAC) in colorectal and appendiceal cancer with peritoneal metastases: results of a multicenter phase Ⅰ trial in the USA[J]. Ann Surg Oncol, 2023, 30(12): 7814-7824.
[37]	ZHANG Y M, WANG S L, DUAN X F, et al. mPEG-PDLLA micelles potentiate docetaxel for intraperitoneal chemotherapy in ovarian cancer peritoneal metastasis[J]. Front Pharmacol, 2022, 13: 861938.
[38]	SHIMIZU T, SONODA H, MURATA S, et al. Hyperthermic intraperitoneal chemotherapy using a combination of mitomycin C, 5-fluorouracil, and oxaliplatin in patients at high risk of colorectal peritoneal metastasis: a phase Ⅰ clinical study[J]. Eur J Surg Oncol, 2014, 40(5): 521-528.
[39]	SUGARBAKER P H. Optimizing regional chemotherapy for epithelial ovarian cancer[J]. J Obstet Gynaecol Res, 2022, 48(6): 1306-1317.
[40]	NADIRADZE G, GIGER-PABST U, ZIEREN J, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with low-dose cisplatin and doxorubicin in gastric peritoneal metastasis[J]. J Gastrointest Surg, 2016, 20(2): 367-373. doi: 10.1007/s11605-015-2995-9 pmid: 26511950
[41]	HELDERMAN R F C P A, LÖKE D R, VERHOEFF J, et al. The temperature-dependent effectiveness of platinum-based drugs mitomycin-C and 5-FU during hyperthermic intraperitoneal chemotherapy (HIPEC) in colorectal cancer cell lines[J]. Cells, 2020, 9(8): 1775.
[42]	BEEHARRY M K, ZHU Z L, LIU W T, et al. Prophylactic HIPEC with radical D2 gastrectomy improves survival and peritoneal recurrence rates for locally advanced gastric cancer: Personal experience from a randomized case control study[J]. BMC Cancer, 2019, 19(1): 932. doi: 10.1186/s12885-019-6125-z pmid: 31533660
[43]	ARJONA-SÁNCHEZ A, ESPINOSA-REDONDO E, GUTIÉRREZ-CALVO A, et al. Efficacy and safety of intraoperative hyperthermic intraperitoneal chemotherapy for locally advanced colon cancer: a phase 3 randomized clinical trial[J]. JAMA Surg, 2023, 158(7): 683-691.
[44]	ZWANENBURG E S, KLAVER C E, WISSELINK D D, et al. Adjuvant hyperthermic intraperitoneal chemotherapy in patients with locally advanced colon cancer (COLOPEC): 5-year results of a randomized multicenter trial[J]. J Clin Oncol, 2024, 42(2): 140-145.
[45]	LIM M C, CHANG S J, PARK B, et al. Survival after hyperthermic intraperitoneal chemotherapy and primary or interval cytoreductive surgery in ovarian cancer: a randomized clinical trial[J]. JAMA Surg, 2022, 157(5): 374-383.
[46]	TALIENTO C, RESTAINO S, SCUTIERO G, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) with cisplatin and doxorubicin in patients with ovarian cancer: a systematic review[J]. Eur J Surg Oncol, 2023, 49(12): 107250.
[47]	REZNICZEK G A, GIGER-PABST U, THAHER O, et al. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for rare gynecologic indications: peritoneal metastases from breast and endometrial cancer[J]. BMC Cancer, 2020, 20(1): 1122. doi: 10.1186/s12885-020-07627-1 pmid: 33213407
[48]	AWAD A, AWAD M, ALAMI M, et al. Successful treatment of pseudomyxoma peritonei (PMP) through cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS-HIPEC): a case report and literature review[J]. Int J Surg Case Rep, 2024, 119: 109656.
[49]	PADMANABHAN N, ISHIBASHI H, NISHIHARA K, et al. Complete pathological response of high grade appendicular neoplasm induced pseudomyxoma peritonei (PMP) after neoadjuvant intra-peritoneal chemotherapy: a case report[J]. Int J Surg Case Rep, 2020, 72: 117-121.
[50]	FENG F L, GAO Q X, WU Y, et al. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy vs cytoreductive surgery alone for intrahepatic cholangiocarcinoma with peritoneal metastases: a retrospective cohort study[J]. Eur J Surg Oncol, 2021, 47(9): 2363-2368.
[51]	KRYH-JENSEN C G, FRISTRUP C W, AINSWORTH A P, et al. What is long-term survival in patients with peritoneal metastasis from gastric, pancreatic, or colorectal cancer? A study of patients treated with systemic chemotherapy and pressurized intraperitoneal aerosol chemotherapy (PIPAC)[J]. Pleura Peritoneum, 2023, 8(4): 147-155.
[52]	JI Z H, PENG K W, YU Y, et al. Current status and future prospects of clinical trials on CRS+HIPEC for gastric cancer peritoneal metastases[J]. Int J Hyperthermia, 2017, 33(5): 562-570.
[53]	GLEHEN O, GILLY F N, ARVIEUX C, et al. Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy[J]. Ann Surg Oncol, 2010, 17(9): 2370-2377. doi: 10.1245/s10434-010-1039-7 pmid: 20336386
[54]	LÓPEZ-BASAVE H N, QUIROZ-SANDOVAL O A, PADILLA-ROSCIANO A E, et al. Papel de la cirugía citorreductora y la quimioterapia intraperitoneal hipertérmica en el tratamiento del cáncer gástrico[J]. Cirugía Y Cirujanos, 2019, 86(3): 936.
[55]	QUÉNET F, ELIAS D, ROCA L, et al. Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial[J]. Lancet Oncol, 2021, 22(2): 256-266. doi: 10.1016/S1470-2045(20)30599-4 pmid: 33476595
[56]	National Comprehensive Cancer Network. NCCN guideline in ovarian cancer/fallopian tube cancer/primary peritoneal cancer (version 1. 2022)[EB/OL]. (2022-03-02) [2024-07-31]. http://www,nccn,org/professionals/physician gls/pdf/ovarian.pdf .
[57]	VAN DRIEL W J, KOOLE S N, SIKORSKA K, et al. Hyperthermic intraperitoneal chemotherapy in ovarian cancer[J]. N Engl J Med, 2018, 378(3): 230-240.
[58]	ARONSON S L, LOPEZ-YURDA M, KOOLE S N, et al. Cytoreductive surgery with or without hyperthermic intraperitoneal chemotherapy in patients with advanced ovarian cancer (OVHIPEC-1): final survival analysis of a randomised, controlled, phase 3 trial[J]. Lancet Oncol, 2023, 24(10): 1109-1118. doi: 10.1016/S1470-2045(23)00396-0 pmid: 37708912
[59]	SUGARBAKER P H. New standard of care for appendiceal epithelial neoplasms and pseudomyxoma peritonei syndrome?[J]. Lancet Oncol, 2006, 7(1): 69-76. doi: 10.1016/S1470-2045(05)70539-8 pmid: 16389186
[60]	CHUA T C, MORAN B J, SUGARBAKER P H, et al. Early- and long-term outcome data of patients with pseudomyxoma peritonei from appendiceal origin treated by a strategy of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy[J]. J Clin Oncol, 2012, 30(20): 2449-2456. doi: 10.1200/JCO.2011.39.7166 pmid: 22614976
[61]	SUGARBAKER P H, VAN DER SPEETEN K. Surgical technology and pharmacology of hyperthermic perioperative chemotherapy[J]. J Gastrointest Oncol, 2016, 7(1): 29-44. doi: 10.3978/j.issn.2078-6891.2015.105 pmid: 26941982
[62]	BREUSA S, ZILIO S, CATANIA G, et al. Localized chemotherapy approaches and advanced drug delivery strategies: a step forward in the treatment of peritoneal carcinomatosis from ovarian cancer[J]. Front Oncol, 2023, 13: 1125868.
[63]	LAGAST N, CARLIER C, CEELEN W P. Pharmacokinetics and tissue transport of intraperitoneal chemotherapy[J]. Surg Oncol Clin N Am, 2018, 27(3): 477-494. doi: S1055-3207(18)30013-9 pmid: 29935684
[64]	MATSUMURA Y, MAEDA H. A new concept for macromolecular therapeutics in cancer chemotherapy: mechanism of tumoritropic accumulation of proteins and the antitumor agent smancs[J]. Cancer Res, 1986, 46(12 Pt 1): 6387-6392. pmid: 2946403
[65]	SMET L D, CEELEN W, REMON J P, et al. Optimization of drug delivery systems for intraperitoneal therapy to extend the residence time of the chemotherapeutic agent[J]. Sci World J, 2013, 2013: 720858.
[66]	WANG X H, ZHANG H, CHEN X H, et al. Overcoming tumor microenvironment obstacles: current approaches for boosting nanodrug delivery[J]. Acta Biomater, 2023, 166: 42-68.
[67]	SUN T, ZHANG G P, NING T T, et al. A versatile theranostic platform for colorectal cancer peritoneal metastases: real-time tumor-tracking and photothermal-enhanced chemotherapy[J]. Adv Sci, 2021, 8(20): e2102256.
[68]	LIANG S, XIAO L Y, CHEN T, et al. Injectable nanocomposite hydrogels improve intraperitoneal co-delivery of chemotherapeutics and immune checkpoint inhibitors for enhanced peritoneal metastasis therapy[J]. ACS Nano, 2024, 18(29): 18963-18979.
[69]	MELAMED J R, YERNENI S S, ARRAL M L, et al. Ionizable lipid nanoparticles deliver mRNA to pancreatic β cells via macrophage-mediated gene transfer[J]. Sci Adv, 2023, 9(4): eade1444.
[70]	GU K, LIANG T, HU L, et al. Intraperitoneal programming of tailored CAR macrophages via mRNA-LNP to boost cancer immunotherapy[M/OL]. (2024-07-30) [2024-08-26]. http://biorxiv.org/lookup/doi/10.1101/2024.07.30.605730 .
[71]	CHEN Z M, TIAN Y, YANG J Y, et al. Modular design of biodegradable ionizable lipids for improved mRNA delivery and precise cancer metastasis delineation in vivo[J]. J Am Chem Soc, 2023, 145(44): 24302-24314.
[72]	HABER T, CORNEJO Y R, ARAMBURO S, et al. Specific targeting of ovarian tumor-associated macrophages by large, anionic nanoparticles[J]. Proc Natl Acad Sci U S A, 2020, 117(33): 19737-19745.
[73]	QU H J, YANG J F, LI S J, et al. Programmed-response cross-linked nanocarrier for multidrug-resistant ovarian cancer treatment[J]. J Control Release, 2023, 357: 274-286.
[74]	WANG K, SHEN R Y, MENG T T, et al. Nano-drug delivery systems based on different targeting mechanisms in the targeted therapy of colorectal cancer[J]. Molecules, 2022, 27(9): 2981.
[75]	HAN X J, GONG C N, YANG Q R, et al. Biomimetic nano-drug delivery system: an emerging platform for promoting tumor treatment[J]. Int J Nanomedicine, 2024, 19: 571-608.
[76]	ZAIKI Y, ISKANDAR A, WONG T W. Functionalized chitosan for cancer nano drug delivery[J]. Biotechnol Adv, 2023, 67: 108200.