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)

Int J Radiat Oncol Biol Phys. 2017 Mar 1;97(3):536-545. doi: 10.1016/j.ijrobp.2016.11.027. Epub 2016 Nov 23.

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 χ2P=.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 IG-IMRT reduces the incidence of acute neutropenia.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / diagnostic imaging
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy
  • Antineoplastic Agents / therapeutic use
  • Bone Marrow*
  • Brachytherapy / methods
  • Carcinoma, Squamous Cell / diagnostic imaging
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy / methods*
  • Cisplatin / therapeutic use*
  • Feasibility Studies
  • Female
  • Gastrointestinal Tract / radiation effects
  • Humans
  • Incidence
  • Middle Aged
  • Neutropenia / epidemiology
  • Neutropenia / prevention & control*
  • Organ Sparing Treatments / methods*
  • Radiation-Sensitizing Agents / therapeutic use*
  • Radiotherapy Dosage
  • Radiotherapy, Image-Guided / methods*
  • Radiotherapy, Intensity-Modulated / methods*
  • Uterine Cervical Neoplasms / diagnostic imaging
  • Uterine Cervical Neoplasms / pathology
  • Uterine Cervical Neoplasms / therapy*

Substances

  • Antineoplastic Agents
  • Radiation-Sensitizing Agents
  • Cisplatin