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)

For the, INTERTECC Study Group

Research output: Contribution to journalArticle

37 Citations (Scopus)

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 χ2 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 IG-IMRT reduces the incidence of acute neutropenia.

Original languageEnglish (US)
Pages (from-to)536-545
Number of pages10
JournalInternational Journal of Radiation Oncology Biology Physics
Volume97
Issue number3
DOIs
StatePublished - Mar 1 2017

Fingerprint

Phase II Clinical Trials
bone marrow
Uterine Cervical Neoplasms
Cisplatin
radiation therapy
Neutropenia
toxicity
Radiotherapy
incidence
Bone Marrow
cancer
grade
Incidence
confidence
Confidence Intervals
intervals
Positron-Emission Tomography
therapy
positrons
leukopenia

ASJC Scopus subject areas

  • Radiation
  • Oncology
  • Radiology Nuclear Medicine and imaging
  • Cancer Research

Cite this

@article{32c20871810b4e0db9e98329e0232a5d,
title = "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 χ2 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 IG-IMRT reduces the incidence of acute neutropenia.",
author = "{For the} and {INTERTECC Study Group} and Mell, {Loren K.} and Igor Sir{\'a}k and Lichun Wei and Rafal Tarnawski and Umesh Mahantshetty and Yashar, {Catheryn M.} and McHale, {Michael T.} and Ronghui Xu and Gordon Honerkamp-Smith and Ruben Carmona and Mary Wright and Williamson, {Casey W.} and Linda Kasaov{\'a} and Nan Li and Stephen Kry and Jeff Michalski and Walter Bosch and William Straube and Julie Schwarz and Jessica Lowenstein and Jiang, {Steve B.} and Saenz, {Cheryl C.} and Steve Plaxe and John Einck and Chonlakiet Khorprasert and Paul Koonings and Terry Harrison and Mei Shi and Mundt, {A. J.}",
year = "2017",
month = "3",
day = "1",
doi = "10.1016/j.ijrobp.2016.11.027",
language = "English (US)",
volume = "97",
pages = "536--545",
journal = "International Journal of Radiation Oncology Biology Physics",
issn = "0360-3016",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Bone Marrow-sparing Intensity Modulated Radiation Therapy With Concurrent Cisplatin For Stage IB-IVA Cervical Cancer

T2 - An International Multicenter Phase II Clinical Trial (INTERTECC-2)

AU - For the

AU - INTERTECC Study Group

AU - Mell, Loren K.

AU - Sirák, Igor

AU - Wei, Lichun

AU - Tarnawski, Rafal

AU - Mahantshetty, Umesh

AU - Yashar, Catheryn M.

AU - McHale, Michael T.

AU - Xu, Ronghui

AU - Honerkamp-Smith, Gordon

AU - Carmona, Ruben

AU - Wright, Mary

AU - Williamson, Casey W.

AU - Kasaová, Linda

AU - Li, Nan

AU - Kry, Stephen

AU - Michalski, Jeff

AU - Bosch, Walter

AU - Straube, William

AU - Schwarz, Julie

AU - Lowenstein, Jessica

AU - Jiang, Steve B.

AU - Saenz, Cheryl C.

AU - Plaxe, Steve

AU - Einck, John

AU - Khorprasert, Chonlakiet

AU - Koonings, Paul

AU - Harrison, Terry

AU - Shi, Mei

AU - Mundt, A. J.

PY - 2017/3/1

Y1 - 2017/3/1

N2 - 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 χ2 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 IG-IMRT reduces the incidence of acute neutropenia.

AB - 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 χ2 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 IG-IMRT reduces the incidence of acute neutropenia.

UR - http://www.scopus.com/inward/record.url?scp=85009986044&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85009986044&partnerID=8YFLogxK

U2 - 10.1016/j.ijrobp.2016.11.027

DO - 10.1016/j.ijrobp.2016.11.027

M3 - Article

VL - 97

SP - 536

EP - 545

JO - International Journal of Radiation Oncology Biology Physics

JF - International Journal of Radiation Oncology Biology Physics

SN - 0360-3016

IS - 3

ER -