General Surgery Resident Brigham and Women's Hospital Boston, Massachusetts, United States
Disclosure: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Participants should be aware of the following financial/non-financial relationships:
Mehida Rojas-Alexandre, MD: I do not have any relevant financial / non-financial relationships with any proprietary interests.
Introduction: Five-year locoregional recurrence rates (LRR) after RPS resection are 25-50%. To overcome the limited utility of chemotherapy and radiotherapy, we designed and previously demonstrated the safety and feasibility of a new generation implantable polymer film eluting the chemotherapy drug paclitaxel locally after surgery mimicking RPS dissection in a porcine surgical model. Here, we hypothesized that Pax-film implantation would decrease local recurrence after resection of patient-derived xenografts (PDX) in a murine model.
Methods: In vivo tumors were established by implanting 2x2x2 mm fragments of dedifferentiated liposarcoma (LP6 ) PDX into the dorsum of 6-8-week-old Nu/J mice. Once primary tumors reached a volume of 500 mm3-1000 mm3, an R1 resection was performed and mice were intraoperatively randomized to 1) no additional treatment (surgery alone), 2) intraperitoneal (IP) paclitaxel 2mg/kg once, 3) unloaded films (no drug control), or 4) Pax-film (500ug). Recurrence and survival were monitored for 45 days after surgery. Survival data were calculated using the Kaplan-Meyer method.
Results: No Pax-film mice developed recurrence within 60 days. In contrast, 2 mice in the surgery alone group, 6 mice in the IP paclitaxel group, and 3 in the unloaded film recurred within 60 days. Correspondingly, mice treated with Pax-film exhibited overall survival with median overall survival (OS) of undefined as compared to 34 days for IP paclitaxel group and undefined for the other treatment groups.
Conclusions: Pax-films resulted in prolonged recurrence-free (RFS) and OS in PDX sarcoma xenografts compared to systemic delivery 60 days after treatment. Polymer-based local delivery of paclitaxel is not only a safe and feasible implant but is also efficacious and has the potential to overcome the high LRR associated with RPS.
Learning Objectives:
Understand the need for local therapeutic approaches for Retroperitoneal Sarcoma
Recognize the complexity and utility of drug-eluting polymer films
Appreciate implantable paclitaxel-eluting polymer as a potential therapeutic approach to overcome the high locoregional recurrence rate of Retroperitoneal Sarcoma
