Tumor Platinum Concentrations and Pathological Responses Following Cisplatin-Containing Chemotherapy in Gastric Cancer Patients
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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.
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.
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.
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.
KeywordsStomach neoplasms Neoadjuvant therapy Platinum Treatment outcome Image cytometry
Epirubicin, cisplatin and 5-fluorouracil
Epirubicin, cisplatin and capecitabine
Docetaxel, oxaliplatin and 5-fluorouracil
Tumor regression grade
Imaging mass cytometry
High-performance liquid chromatography mass spectrometry
Non-small cell lung cancer
We thank Jing Xu for valuable technical assistance.
EC and YC conceived and designed the study and analyzed the data. QC performed IMC analysis. MC analyzed the trichrome and Ki67 data. WZ performed tissue platinum analysis. All authors made substantial contributions towards drafting the manuscript, reviewed the final manuscript for intellectual content, and authorized the submission. All authors read and approved the final manuscript.
This study was funded by the Princess Margaret Cancer Foundation.
Compliance with Ethical Standards
This study was approved by the Research Ethics Board at the University Health Network, Toronto, Canada and conducted in compliance with relevant Ethics Standards.
Conflict of Interest
Qing Chang and Olga Ornatsky are employees of Fluidigm Canada Inc. Olga Ornatsky is one of the co-founders of DVS Sciences Inc. (now part of Fluidigm) that invented, developed and manufactures mass cytometry technologies, including the Helios CyTOF system, the Imaging Mass Cytometer and metal-conjugated reagents.
No other authors declared any potential conflicts of interest.
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