High tumor interstitial fluid pressure identifies cervical cancer patients with improved survival from radiotherapy plus cisplatin versus radiotherapy alone

Michael F. Milosevic, Melania Pintilie, David W. Hedley, Robert G. Bristow, Bradly G. Wouters, Amit M. Oza, Stephane Laframboise, Richard P. Hill, Anthony W. Fyles

Research output: Contribution to journalArticlepeer-review

Abstract

Radiotherapy (RT) with concurrent cisplatin (CRT) is standard treatment for locally advanced cervical cancer. However, not all patients benefit from the addition of cisplatin to RT alone. This study explored the value of pretreatment tumor interstitial fluid pressure (IFP) and hypoxia measurements as predictors of cisplatin response in 291 patients who were treated with RT (1994-1998) or RT plus concurrent cisplatin (1999-2009). Clinical characteristics were similar between the two groups, apart from a greater proportion of patients with pelvic lymph node metastases and hypoxic tumors in the CRT cohort. Patients were followed for a median duration of 5.6 years. Information about recurrence and survival was recorded prospectively. The addition of cisplatin to RT improved survival compared to treatment with RT alone (HR 0.61, p = 0.0097). This improvement was confined to patients with high-IFP tumors at diagnosis (HR 0.40, p = 0.00091). There was no benefit of adding cisplatin in those with low-IFP tumors (HR 1.05, p = 0.87). There was no difference in the effectiveness of cisplatin in patients with more or less hypoxic tumors. In conclusion, patients with locally advanced cervical cancer and high tumor IFP at diagnosis have greater benefit from the addition of cisplatin to RT than those with low IFP. This may reflect high tumor cell proliferation, which is known to influence IFP, local tumor control and patient survival. What's new? Radiotherapy with concurrent cisplatin chemotherapy is standard treatment for locally advanced cervical cancer. However, the majority of patients will not benefit from the addition of chemotherapy. In this study, the authors found that patients whose tumors had high interstitial fluid pressure (IFP) prior to treatment experienced improved local tumor control and greater overall survival with the combined-modality treatment than those with low IFP. This easily-measured biomarker may thus provide a valuable predictive assay for a patient's response to cisplatin, helping to avoid over-treatment and reducing unnecessary side effects.

Original languageEnglish
Pages (from-to)1692-1699
Number of pages8
JournalInternational Journal of Cancer
Volume135
Issue number7
DOIs
Publication statusPublished - 1 Oct 2014

Keywords

  • cervical cancer
  • cisplatin
  • hypoxia
  • interstitial fluid pressure (IFP)
  • radiotherapy

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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