Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer: An International Multicenter Phase II Clinical Trial (INTERTECC-2)
Abstract
Purpose: To test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer. Methods and Materials: We enrolled patients with stage IB-IVA cervical carcinoma in a single-arm phase II trial involving 8 centers internationally.
All patients received weekly cisplatin concurrently with once-daily IMRT, followed by intracavitary brachytherapy, as indicated. The primary endpoint was the occurrence of either acute grade >= 3 neutropenia or clinically significant GI toxicity within 30 days of completing chemoradiation therapy.
A preplanned subgroup analysis tested the hypothesis that positron emission tomography-based image-guided IMRT (IG-IMRT) would lower the risk of acute neutropenia. We also longitudinally assessed patients' changes in quality of life.
Results: From October 2011 to April 2015, 83 patients met the eligibility criteria and initiated protocol therapy. The median follow-up was 26.0 months.
The incidence of any primary event was 26.5% (95% confidence interval [CI] 18.2%-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (P = .012). The incidence of grade >= 3 neutropenia and clinically significant GI toxicity was 19.3% (95% CI 12.2%-29.0%) and 12.0% (95% CI 6.7%-20.8%), respectively.
Compared with patients treated without IG-IMRT (n = 48), those treated with IG-IMRT (n = 35) had a significantly lower incidence of grade >= 3 neutropenia (8.6% vs 27.1%; 2-sided chi(2) P = .035) and nonsignificantly lower incidence of grade >= 3 leukopenia (25.7% vs 41.7%; P = .13) and any grade >= 3 hematologic toxicity (31.4% vs 43.8%; P = .25). Conclusions: IMRT reduces acute hematologic and GI toxicity compared with standard treatment, with promising therapeutic outcomes.
Positron emission tomography IGIMRT reduces the incidence of acute neutropenia.