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| Trans-lymphatic Chemotherapy Controls Lymphatic Metastasis and Prolongs Survival in an Orthotopic Lung Cancer Model |
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Jiang Liu1, Ming Li1, Michael R. Johnston2; 1Princess Margaret Hospital / University Health Network, Toronto, ON, Canada; 2Thoracic Surgery, Queen Elizabeth II Health Sciences Centre, Dalhousie University, Halifax, NS, Canada Objective: Lymphatic metastasis is a critical prognostic factor in lung cancer and poses a significant challenge to treat. We developed an implantable trans-lymphatic drug delivery system which can effectively control lymphatic tumor metastasis. In the present study we investigated the survival benefit of the system as an adjuvant to surgery in an orthotopic lung cancer model. Methods: A gelatin sponge device containing polylactide-co-glicolide paclitaxel (PLGA-PTX) microspheres was synthesized to contain 20 mg PLGA-PTX microparticles (7% drug loading, 1.4 mg PTX/each). A placebo control sponge containing equivalent amounts of blank PLGA microspheres was similarly made. The lung cancer model was established in nude rats by endobronchial implantation of one million NCI-H460 human lung cancer cells into the left lung via a tracheotomy. Fourteen days following tumor implantation, the lung was resected by left pneumonectomy. Animals were treated intraoperatively with either intrapleural implantation of a PLGA-PTX gelatin sponge (n=16), or a placebo sponge (n=15). Postoperative survival time and tumor recurrences were measured. The incidence of tumor recurrence at the resection margin, lymph node metastasis and lymph node weight were compared. Results: Three control animals, but no treated animals, developed tumor at the resection margin. All control animals developed tumor recurrence in mediastinal lymph nodes. 4 of 15 (27%) of treated animals developed mediastinal lymph node metastasis. Mean lymph node weight, reflecting the tumor burden, was 0.35±0.15 g (n=16) and 0.13±0.16 g (n=4) for control and treated groups respectively (p<0.01). PLGA-PTX microspheres were evident microscopically in the lymph nodes. The mean survival time (mean±SE) for control animals and treated animals was 27.4±0.83 days and 42±2.87 days respectively (p<0.01). Conclusion: This novel trans-lymphatic drug delivery system can effectively control lymphatic metastasis and local tumor recurrence. It also prolongs lung cancer survival in an adjuvant orthotopic lung cancer model. The system offers a unique therapeutic modality as an intraoperative adjuvant to lung cancer resection. Back to 2010 Annual Meeting Back to Program Outline Back to Main Program |
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