Application of Intraperitoneal Chemotherapy in Mesothelioma cancer patients

Application of Intraperitoneal Chemotherapy 

Repeated application of intraperitoneal therapy (HIPEC and/or IP) has become an area of interest and maybe a simple but impactful strategy to help improve outcomes in MPM. In particular, patients with major diseases defined by high PCI (>20-25) remain a high-risk group, and efforts to improve outcomes with this strategy have been explored. 

One strategy is a two-stage procedure in which the patient undergoes a limited debulked with resection of the omentum and a large tumor but avoids a large resection (incomplete debulking) joining HIPEC. The next patient received adjuvant chemotherapy and returned to OR for a second CRS/HIPEC. Heller et al. showed a median relapse-free survival of 38.5 months for optimally treated patients with MPM undergoing two-stage CRS/HIPEC. 

Their study found that completeness of cytoreduction scores < CC1 in the first and second surgeries resulted in a median OS of 6.65 years (95% Cl 5.03-14.41). Tumor histology is not a significant factor in recurrence, but biphasic and sarcomatoid tumors are a minority of patients. In this study, only lesions larger than 0.5 cm were resected, providing evidence of the efficacy of HIPEC for small and microscopic diseases (Heller et al. 2017).

The concept of recurrent intraperitoneal chemotherapy has also been explored with normothermic intraperitoneal chemotherapy (NIPEC) after definitive CRS/HIPEC in 29 patients. This is conceptually similar to the use of IP chemotherapy after CRS in ovarian cancer (Armstrong et al. 2006). 

This early experience was reported by Sugarbaker et al. showed that CRS / HIPEC with nipec improved survival despite high preoperative PCI and reported 5-year survival was 75%. Similarly, in this treatment model, the CC score is relevant because the survival benefit was only observed in optimally debugged CC0, and CC-1 patients (Sugarbaker and Chang 2017).

The focus of laboratory research to identify the biological mechanisms involved in peritoneal mesothelioma will lead to new therapies that help improve survival (Esquivel et al. 2007). In addition, efforts to develop clinical trials to help identify the best combination and sequencing of these therapies are being designed. 

In a subset of patients, CRS / HIPEC and systemic chemotherapy have significantly improved outcomes and prolonged survival, but continued research is needed to improve patient selection and improve outcomes for all patients with MPM.

In conclusion, significant progress has been made through a solid understanding of the biology of peritoneal metastases and basic peritoneal therapies. This work has produced better results for patients with peritoneal mesothelioma patients, and for a subset, long-term survival can be achieved. 

CRS / HIPEC is the most effective current therapy in the management of peritoneal mesothelioma. Most patients will also receive chemotherapy as part of their treatment. Further progress is still needed in optimizing outcomes, patient selection, and the development of new effective therapies in mesothelioma.

Source

Harvey I. Pass, Nicholas Vogelzang, Michele Carbone - Malignant Mesothelioma_ Pathogenesis, Diagnosis, and Translational Therapies-Springer (2005)

Mary Hesdorffer, Gleneara E. Bates-Pappas - Caring for Patients with Mesothelioma_ Principles and Guidelines-Springer International Publishing (2019)

Bruce W S Robinson, A Philippe Chahinian - Mesothelioma (2002).

Alexander HR Jr, et al. Treatment factors associated with long-term survival after cytoreductive surgery and regional chemotherapy for patients with malignant peritoneal mesothelioma. Surgery. 2013;153(6):779-86.

Armstrong DK, et al. Intraperitoneal cisplatin and paclitaxel in ovarian cancer. N Engl J Med. 2006;354(1):34^13.

Chua TC, Yan TD, Morris DL. Outcomes of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma: the Australian experience. J Surg Oncol. 2009;99(2): 109-13.


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