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Tumor Platinum Concentrations and Pathological Responses Following Cisplatin-Containing Chemotherapy in Gastric Cancer Patients

  • Yanshuo Cao
  • Qing Chang
  • Michael Cabanero
  • Wenjiang Zhang
  • Sara Hafezi-Bakhtiari
  • David Hedley
  • Gail Darling
  • Fayez Quereshy
  • Raymond Jang
  • Elena Elimova
  • Jennifer Knox
  • Olga Ornatsky
  • Stefano Serra
  • Eric ChenEmail author
Original Research

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.

Keywords

Stomach neoplasms Neoadjuvant therapy Platinum Treatment outcome Image cytometry 

Abbreviations

GEJ

Gastroesophageal junction

ECF

Epirubicin, cisplatin and 5-fluorouracil

HR

Hazard ratio

ECX

Epirubicin, cisplatin and capecitabine

FLOT

Docetaxel, oxaliplatin and 5-fluorouracil

CT

Computer tomography

FFPE

Formalin-fixed, paraffin-embedded

TRG

Tumor regression grade

IMC

Imaging mass cytometry

HPLC-MS/MS

High-performance liquid chromatography mass spectrometry

PR

Partial response

SD

Stable disease

NSCLC

Non-small cell lung cancer

ND

Not detectable

NA

Not available

Notes

Acknowledgments

We thank Jing Xu for valuable technical assistance.

Author’s Contributions

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.

Funding

This study was funded by the Princess Margaret Cancer Foundation.

Compliance with Ethical Standards

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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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Yanshuo Cao
    • 1
  • Qing Chang
    • 2
  • Michael Cabanero
    • 3
  • Wenjiang Zhang
    • 1
  • Sara Hafezi-Bakhtiari
    • 3
  • David Hedley
    • 1
  • Gail Darling
    • 4
  • Fayez Quereshy
    • 4
  • Raymond Jang
    • 1
  • Elena Elimova
    • 1
  • Jennifer Knox
    • 1
  • Olga Ornatsky
    • 2
  • Stefano Serra
    • 3
  • Eric Chen
    • 1
    Email author
  1. 1.Division of Medical Oncology and Hematology, Princess Margaret Cancer CentreUniversity Health NetworkTorontoCanada
  2. 2.Fluidigm Canada Inc.MarkhamCanada
  3. 3.Laboratory Medicine ProgramUniversity Health NetworkTorontoCanada
  4. 4.Division of SurgeryUniversity Health NetworkTorontoCanada

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