title: High tumor interstitial fluid pressure identifies cervical cancer patients with improved survival from radiotherapy plus cisplatin versus radiotherapy alone.
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.
authors.affiliation: Radiation Medicine Program, Princess Margaret Cancer Center, University Health Network, Toronto, Canada; Department of Radiation Oncology, University of Toronto, Toronto, Canada.
authors.forename: Michael F
authors.initials: MF
authors.lastname: Milosevic
authors.forename: Melania
authors.initials: M
authors.lastname: Pintilie
authors.forename: David W
authors.initials: DW
authors.lastname: Hedley
authors.forename: Robert G
authors.initials: RG
authors.lastname: Bristow
authors.forename: Bradly G
authors.initials: BG
authors.lastname: Wouters
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Stephane
authors.initials: S
authors.lastname: Laframboise
authors.forename: Richard P
authors.initials: RP
authors.lastname: Hill
authors.forename: Anthony W
authors.initials: AW
authors.lastname: Fyles
mesh_terms: D000230:Adenocarcinoma / Q000401:mortality / Q000556:secondary / Q000628:therapy; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000556:secondary / Q000628:therapy; D059248:Chemoradiotherapy / Q000401:mortality*; D002945:Cisplatin / Q000627:therapeutic use*; D045604:Extracellular Fluid / Q000737:chemistry* / Q000187:drug effects / Q000528:radiation effects; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000860:Hypoxia; D008207:Lymphatic Metastasis; D009364:Neoplasm Recurrence, Local / Q000401:mortality* / Q000473:pathology / Q000628:therapy; D009367:Neoplasm Staging; D011312:Pressure; D011379:Prognosis; D011446:Prospective Studies; D011878:Radiotherapy / Q000401:mortality*; D015996:Survival Rate; D002583:Uterine Cervical Neoplasms / Q000401:mortality* / Q000473:pathology / Q000628:therapy
chemical_list: D000970:Antineoplastic Agents; D002945:Cisplatin
keywords: cervical cancer; cisplatin; hypoxia; interstitial fluid pressure (IFP); radiotherapy