Evaluation of Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Stage III Epithelial Ovarian Cancer

Lei, Ziying; Wang, Yue; Wang, Jiahong; Wang, Ke; Tian, Jie; Zhao, Ying; Chen, Lipai; Wang, Jin; Luo, Jiali; Jia, Manman; Tang, Hua; He, Qiwei; Liao, Quanxing; Yang, Xiaohan; Guan, Tianwang; Wang, Li; Cui, Shuzhong

doi:10.1001/jamanetworkopen.2020.13940

Cited by 66 publications

(54 citation statements)

References 37 publications

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“…Examples of this concept are provided in Figure 3. This finding has potential implications for efficacy of regional therapeutic strategies, such as intraperitoneal administration of chemotherapy in women with advanced epithelial ovarian carcinomas (65). One example of the potential importance of TNT-mediated cell tethering of spheroids is that it would facilitate direct TNT-specific cell-to-cell communication in the evolution of resistance to this treatment, in a more specific manner than EVs can perform in this fluid-filled environment.…”

Section: Peritoneal Cancers Including Ovarian Carcinoma and Malignanmentioning

confidence: 98%

A Ticket to Ride: The Implications of Direct Intercellular Communication via Tunneling Nanotubes in Peritoneal and Other Invasive Malignancies

Lou

2020

Front. Oncol.

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It is well established that the role of the tumor microenvironment (TME) in cancer progression and therapeutic resistance is crucial, but many of the underlying mechanisms are still being elucidated. Even with better understanding of molecular oncology and identification of genomic drivers of these processes, there has been a relative lag in identifying and appreciating the cellular drivers of both invasion and resistance. Intercellular communication is a vital process that unifies and synchronizes the diverse components of the tumoral infrastructure. Elucidation of the role of extracellular vesicles (EVs) over the past decade has cast a brighter light on this field. And yet even with this advance, in addition to diffusible soluble factor-mediated paracrine and endocrine cell communication as well as EVs, additional niches of intratumoral communication are filled by other modes of intercellular transfer. Tunneling nanotubes (TNTs), tumor microtubes (TMs), and other similar intercellular channels are long filamentous actin-based cellular conduits (in most epithelial cancer cell types, ~15-500 µm in length; 50–1000+ nm in width). They extend and form direct connections between distant cells, serving as conduits for direct intercellular transfer of cell cargo, such as mitochondria, exosomes, and microRNAs; however, many of their functional roles in mediating tumor growth remain unknown. These conduits literally create a physical bridge to create a syncytial network of dispersed cells amidst the intercellular stroma-rich matrix. Emerging evidence suggests that they provide a cellular mechanism for induction and emergence of drug resistance and contribute to increased invasive and metastatic potential. They have been imaged in vitro and also in vivo and ex vivo in tumors from human patients as well as animal models, thus not only proving their existence in the TME, but opening further speculation about their exact role in the dynamic niche of tumor ecosystems. TNT cellular networks are upregulated between cancer and stromal cells under hypoxic and other conditions of physiologic and metabolic stress. Furthermore, they can connect malignant cells to benign cells, including vascular endothelial cells. The field of investigation of TNT-mediated tumor-stromal, and tumor-tumor, cell-cell communication is gaining momentum. The mixture of conditions in the microenvironment exemplified by hypoxia-induced ovarian cancer TNTs playing a crucial role in tumor growth, as just one example, is a potential avenue of investigation that will uncover their role in relation to other known factors, including EVs. If the role of cancer heterocellular signaling via TNTs in the TME is proven to be crucial, then disrupting formation and maintenance of TNTs represents a novel therapeutic approach for ovarian and other similarly invasive peritoneal cancers.

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Section: Peritoneal Cancers Including Ovarian Carcinoma and Malignanmentioning

confidence: 98%

A Ticket to Ride: The Implications of Direct Intercellular Communication via Tunneling Nanotubes in Peritoneal and Other Invasive Malignancies

Lou

2020

Front. Oncol.

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“…Lei et al [49] perfomed a cohort study from January 2010 to May 2017 at 5 high-volume institutions in China to compare survival outcomes between PCS with HIPEC vs. PCS alone for patients with stage III epithelial ovarian cancer. A total of 584 patients with stage III primary epithelial ovarian cancer were treated with either PCS alone or PCS with HIPEC.…”

Section: Review and Discussionmentioning

confidence: 99%

HIPEC for Ovarian Cancer: A Controversial Discussion

Friedrich¹,

Friedrich²,

Kraft³

et al. 2021

Ovarian Cancer - Updates in Tumour Biology and Therapeutics [Working Title]

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Peritoneal carcinomatosis is a sign of advanced disease of ovarian cancer. The prognosis of ovarian cancer is significantly improved after cytoreductive surgery with complete tumor debulking followed by platin based chemotherapy. If cytoreductive surgery results in a tumor free situation with remaining tumor less than 0.25 cm, HIPEC may further improve prognosis. Materials and methods: The results of the Krefeld study are presented and the literature is reviewed according to overall survival and progression free survival with or without HIPEC. In the Krefeld study, patients with ovarian cancer and peritoneal carcinomatosis underwent cytoreductive surgery. In patients with optimal tumor debulking, HIPEC was performed. The peri- and postoperative course was observed. Adverse events were recorded after the Clavien-Dindo classification. Results: 43 patients were treated with cytoreductive surgery and HIPEC. In all patients an optimal cytoreductive situation with remaining tumor less than 0.25 cm was achieved. HIPEC was performed with a cisplatin solution (50 mg/m2) at 41°C. The median age of the patients was 56 years (range: 32–74 years), the median peritoneal cancer index (PCI) was 13 (range: 4–21), the median operation time was 356 minutes (range: 192–507 minutes). The median time to postoperative systemic treatment with chemotherapy was 29 days (range 21–70). There was no postoperative surgically associated death. No adverse events were recorded in 16 (37.2%) of 43 patients, no grade III or IV adverse events were reported for 33 (76.7%) patients, and no grade IV adverse events were reported for 41 (95.3%) patients. Grade III adverse events occured in 19 (44.2%) of the 43 patients; a total of 29 grade III adverse events were reported in these 19 patients. Grade IV adverse events occured in 3 (7.0%) of the 43 patients; a total of 3 grade IV adverse events were reported. Two of them resulted in return to the operating room. This was a fistula of the distal small bowel caused by drainage and a revision of wound infection. Conclusion: In ovarian cancer multiple surgical procedures may be necessary in order to have macroscopically eradicated tumor tissue. Combined with HIPEC, this seems to have positive effects on the survival of patients with peritoneal carcinomatosis. Since we have no marked additional adverse events caused by HIPEC in our case series, HIPEC seems to be an additional treatment option of peritoneal carcinomatosis in ovarian cancer. This statement is strengthened by the literature review in that metaanalysis show significant improved OAS and PFS.

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“…International groups agree that these women should only receive HIPEC within a clinical trial 16 . A recent retrospective cohort study of 584 women who underwent up‐front surgery for stage III ovarian cancer showed significantly improved survival in the HIPEC arm (49.8 months vs 34.0 months, HR = 0.63, 95%CI, 0.49–0.82, P < 0.001) 17 . However, caution is required in interpreting these results due to potential confounders of a non‐randomised trial.…”

Section: What Is the Current Evidence For Hipec For The Treatment Of mentioning

confidence: 99%

HIPEC: Turning up the heat on ovarian cancer

Farrell

Burling

2021

Aust NZ J Obst Gynaeco

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Clinical trials of heated intraperitoneal chemotherapy (HIPEC ) for the treatment of advanced ovarian cancer are showing promising survival outcomes. HIPEC has the potential to eliminate ovarian cancer cells from peritoneal surfaces more effectively than systemic chemotherapy through enhanced pharmacokinetic and hyperthermia effects. However, many questions remain to be answered, particularly regarding the true place of HIPEC in the current era of new and effective targeted treatments. Concerns around the potential for increased morbidity, adverse effects on quality of life, and increased resource use following HIPEC use, can only be properly evaluated with ongoing high‐quality clinical trials.

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Evaluation of Cytoreductive Surgery With or Without Hyperthermic Intraperitoneal Chemotherapy for Stage III Epithelial Ovarian Cancer

Cited by 66 publications

References 37 publications

A Ticket to Ride: The Implications of Direct Intercellular Communication via Tunneling Nanotubes in Peritoneal and Other Invasive Malignancies

A Ticket to Ride: The Implications of Direct Intercellular Communication via Tunneling Nanotubes in Peritoneal and Other Invasive Malignancies

HIPEC for Ovarian Cancer: A Controversial Discussion

HIPEC: Turning up the heat on ovarian cancer

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