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• W1968045230 abstract "Preoperative radiotherapy (RT) is commonly used to treat localised soft-tissue sarcomas (STS). Hypoxia is an important determinant of radioresistance. Whether antiangiogenic therapy can ‘normalise’ tumour vasculature, thereby improving oxygenation, remains unknown. Two cohorts were prospectively enrolled. Cohort A evaluated the implications of hypoxia in STS, using the hypoxic tracer 18F-azomycin arabinoside (FAZA-PET). In cohort B, sunitinib was added to preoperative RT in a dose-finding phase 1b/2 design. In cohort A, 13 out of 23 tumours were hypoxic (FAZA-PET), correlating with metabolic activity (r2=0.85; P<0.001). Two-year progression-free (PFS) and overall (OS) survival were 61% (95% CI: 0.44–0.84) and 87% (95% CI: 0.74–1.00), respectively. Hypoxia was associated with radioresistance (P=0.012), higher local recurrence (Hazard ratio (HR): 10.2; P=0.02), PFS (HR: 8.4; P=0.02), and OS (HR: 41.4; P<0.04). In Cohort B, seven patients received sunitinib at dose level (DL): 0 (50 mg per day for 2 weeks before RT; 25 mg per day during RT) and two patients received DL: −1 (37.5 mg per day for entire period). Dose-limiting toxicities were observed in 4 out of 7 patients at DL 0 and 2 out of 2 patients at DL −1, resulting in premature study closure. Although there was no difference in PFS or OS, patients receiving sunitinib had higher local failure (HR: 8.1; P=0.004). In STS, hypoxia is associated with adverse outcomes. The combination of sunitinib with preoperative RT resulted in unacceptable toxicities, and higher local relapse rates." @default.
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• W1968045230 date "2014-10-16" @default.
• W1968045230 modified "2023-10-18" @default.
• W1968045230 title "A phase Ib/II translational study of sunitinib with neoadjuvant radiotherapy in soft-tissue sarcoma" @default.
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• W1968045230 doi "https://doi.org/10.1038/bjc.2014.537" @default.
• W1968045230 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/4264446" @default.
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