Yanshuo Cao1, Qing Chang2, Michael Cabanero3, Wenjiang Zhang1, Sara Hafezi-Bakhtiari3, David Hedley1, Gail Darling4, Fayez Quereshy4, Raymond Jang1, Elena Elimova1, Jennifer Knox1, Olga Ornatsky2, Stefano Serra3, Eric Chen5. 1. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Room 5-719, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. 2. Fluidigm Canada Inc., Markham, Canada. 3. Laboratory Medicine Program, University Health Network, Toronto, Canada. 4. Division of Surgery, University Health Network, Toronto, Canada. 5. Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University Health Network, Room 5-719, 610 University Avenue, Toronto, ON, M5G 2M9, Canada. eric.chen@uhn.ca.
Abstract
PURPOSE: There is a wide range in tumor response following preoperative chemotherapy in locally advanced gastric or gastroesophageal junction cancers. We investigated the relationship between tumor platinum levels and pathological responses in these patients. METHODS: Tumor and adjacent normal tissues were retrieved. Pathological responses were assessed per standard criteria. Tissue platinum concentrations were determined with high-performance liquid chromatography mass spectrometry. Platinum distribution in tissue components was evaluated with imaging mass cytometry. Collagen content was evaluated using trichrome staining. RESULTS: Surgical specimens from 10 patients were available. Surgery was performed at a median time of 49 days (range: 28-72) after the last cycle of chemotherapy. The mean platinum level in tumor tissue in patients with any response was significantly higher than in those with no response (893 ± 460 vs. 38.8 ± 8.8 pg, P = 0.007), so was the collagen content (37.4 ± 6.8 vs. 11.5 ± 8.6%, P < 0.05). Platinum preferentially bound to collagen. CONCLUSIONS: Platinum was detectable in surgical specimens up to 72 days after preoperative chemotherapy. Higher tumor platinum concentration correlated with improved pathological response. Collagen binding potentially explained the high interpatient variability in tumor platinum concentrations.
PURPOSE: There is a wide range in tumor response following preoperative chemotherapy in locally advanced gastric or gastroesophageal junction cancers. We investigated the relationship between tumorplatinum levels and pathological responses in these patients. METHODS:Tumor and adjacent normal tissues were retrieved. Pathological responses were assessed per standard criteria. Tissue platinum concentrations were determined with high-performance liquid chromatography mass spectrometry. Platinum distribution in tissue components was evaluated with imaging mass cytometry. Collagen content was evaluated using trichrome staining. RESULTS: Surgical specimens from 10 patients were available. Surgery was performed at a median time of 49 days (range: 28-72) after the last cycle of chemotherapy. The mean platinum level in tumor tissue in patients with any response was significantly higher than in those with no response (893 ± 460 vs. 38.8 ± 8.8 pg, P = 0.007), so was the collagen content (37.4 ± 6.8 vs. 11.5 ± 8.6%, P < 0.05). Platinum preferentially bound to collagen. CONCLUSIONS:Platinum was detectable in surgical specimens up to 72 days after preoperative chemotherapy. Higher tumorplatinum concentration correlated with improved pathological response. Collagen binding potentially explained the high interpatient variability in tumorplatinum concentrations.
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