Metastatic renal cell carcinoma: relationship between initial metastasis hypoxia, change after 1 month's sunitinib, and therapeutic response: an 18F-fluoromisonidazole PET/CT study

Florent Hugonnet, Laure Fournier, Jacques Medioni, Corinne Smadja, Elif Hindié, Virginie Huchet, Emmanuel Itti, Charles-André Cuenod, Gilles Chatellier, Stéphane Oudard, Marc Faraggi
Journal of Nuclear Medicine 2011, 52 (7): 1048-55

UNLABELLED: The aims of this cohort study were to evaluate initial tumor hypoxia in metastatic renal cell carcinoma (mRCC) and its changes after sunitinib treatment, using (18)F-fluoromisonidazole PET/CT, and investigate the possible prognostic value of initial tumor hypoxia or its changes under sunitinib therapy.

METHODS: Antiangiogenic-naive patients with mRCC were prospectively enrolled in this cohort study. Before initiation of sunitinib, CT defined up to 10 targets that were assessed at 1 and 6 mo according to the response evaluation criteria in solid tumors (RECIST). Pretreatment target uptake of (18)F-fluoromisonidazole was compared with uptake at 1 mo. Targets were considered hypoxic when their maximal standard uptake value was above mean blood value + 2 SDs. Hypoxic volumes were also computed. Relationships between initial hypoxia status, initial degree of hypoxia, its change at 1 mo, and overall or progression-free survival (OS and PFS, respectively) were assessed by survival analysis.

RESULTS: Fifty-three patients were included. Median follow-up was 16.8 mo. (18)F-fluoromisonidazole uptake significantly decreased in initially hypoxic target metastases but did not change in others (-22%, P < 10(-4), vs. +1.5%, P = 0.77; P = 10(-3) between groups). Seventy-five percent of patients with hypoxic metastases were free of progressive disease at 4.8 mo (95% confidence interval, 2.99-11.83), compared with 11.3 mo (95% confidence interval, 3.08-36.9) for other patients (P = 0.02), whereas OS was not significantly different. Changes in tumor hypoxia were not related to PFS or OS.

CONCLUSION: Sunitinib reduced hypoxia in initially hypoxic RECIST target metastases but did not induce significant hypoxia in nonhypoxic RECIST target metastases. Patients with initially hypoxic targets have shorter PFS than others.

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