Bone Marrow-Sparing Intensity Modulated Radiation Therapy with Concurrent Cisplatin for Stage Ib-Iva Cervical Cancer: An International Multi-Center Phase Ii Clinical Trial (Intertecc-2)

Publication date: Available online 23 November 2016
Source:International Journal of Radiation Oncology*Biology*Physics
Author(s): Loren K. Mell, Igor Sirák, Lichun Wei, Rafal Tarnawski, Umesh Mahantshetty, Catheryn M. Yashar, Michael T. McHale, Ronghui Xu, Gordon Honerkamp-Smith, Ruben Carmona, Mary Wright, Casey W. Williamson, Linda Kasaová, Nan Li, Stephen Kry, Jeff Michalski, Walter Bosch, William Straube, Julie Schwarz, Jessica Lowenstein, Steve B. Jiang, Cheryl C. Saenz, Steve Plaxe, John Einck, Chonlakiet Khorprasert, Paul Koonings, Terry Harrison, Mei Shi, A.J. Mundt
PurposeTo test the hypothesis that intensity modulated radiation therapy (IMRT) reduces acute hematologic and gastrointestinal (GI) toxicity for patients with locoregionally advanced cervical cancer.MethodsWe enrolled patients with stage IB-IVA cervical carcinoma on a single-arm phase II trial involving eight 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 chemoradiotherapy. A pre-planned subgroup analysis tested the hypothesis that positron emission tomography (PET)-based image-guided IMRT (IG-IMRT) lowers the risk of acute neutropenia. We also longitudinally assessed changes in quality of life.ResultsFrom October 2011 to April 2015, 83 patients met eligibility criteria and initiated protocol therapy. Median follow-up was 26.0 months. The incidence of any primary event was 26.5% (95% CI, 18.2-36.9%), significantly lower than the 40% incidence hypothesized a priori from historical data (p=0.012). The incidences of grade ≥ 3 neutropenia and clinically significant GI toxicity were 19.3% (95% CI, 12.2-29.0%) and 12.0% (95% CI, 6.7-20.8%), respectively. Compared to patients treated without IG-IMRT (N=48), patients treated with IG-IMRT (N=35) had significantly lower grade ≥ 3 neutropenia (8.6% vs. 27.1%, 2-sided chi-square p=0.035), and non-significantly lower grade ≥ 3 leukopenia (25.7% vs. 41.7%, p=0.13) and any grade ≥ 3 hematologic toxicity (31.4% vs. 43.8%, p=0.25).ConclusionIMRT reduces acute hematologic and GI toxicity compared to standard treatment, with promising therapeutic outcomes. PET-guided IMRT reduces acute neutropenia.

Teaser

This was an international phase II trial to test the hypothesis that IMRT reduces acute toxicity for locoregionally advanced cervical cancer. In 83 patients enrolled, acute gastrointestinal was significantly reduced with both IMRT and PET-guided bone marrow sparing IMRT (IG-IMRT) compared to historical controls. Neutropenia was significantly reduced in patients treated with IG-IMRT. We conclude that IMRT reduces acute toxicity compared to standard treatment in this population, and that IG-IMRT warrants testing in randomized trials.


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