Modeling the Impact of Cardiopulmonary Irradiation on Overall Survival in NRG Oncology Trial RTOG 0617

Clinical Cancer Research - Tập 26 Số 17 - Trang 4643-4650 - 2020
Maria Thor1, Joseph O. Deasy1, Chen Hu2, Elizabeth Gore3, Voichita Bar‐Ad4, Clifford G. Robinson5, Matthew Wheatley6, Jung Hun Oh1, Jeffrey A. Bogart7, Yolanda I. Garces8, Vivek S. Kavadi9, Samir Narayan10, Puneeth Iyengar11, Jacob S. Witt12, James W. Welsh13, Cristopher D. Koprowski14, James M. Larner15, Ying Xiao16, Jeffrey D. Bradley17
11Department of Medical Physics, Memorial Sloan Kettering Cancer Center, New York, New York.
22NRG Oncology Statistics and Data Management Center, Philadelphia, Pennsylvania.
33Zablocki Veterans Administration Medical Center, Milwaukee, Wisconsin.
44Thomas Jefferson University Hospital, Philadelphia, Pennsylvania.
55Siteman Cancer Center at Washington University, St. Louis, Missouri.
66Mercy San Juan Medical Center Dignity Health, Carmichael, California.
77State University of New York Upstate Medical University, Syracuse, New York.
88Mayo Clinic, Rochester, Minnesota.
99Texas Oncology Cancer Center Sugar Land, Sugar Land, Texas.
1010Saint Joseph Mercy Hospital, Ypsilanti, Michigan.
1111UT Southwestern/Simmons Cancer Center, Dallas, Texas.
1212University of Wisconsin-Madison (accruals under Washington University), Madison, Wisconsin.
1313University of Texas MD Anderson Cancer Center, Houston, Texas.
1414Christiana Care Health System-Christiana Hospital, Newark, Delaware.
1515University of Virginia Cancer Center, Charlottesville, Virginia.
1616University of Pennsylvania, Philadelphia, Pennsylvania.
1717Emory University School of Medicine, Atlanta, Georgia.

Tóm tắt

Abstract Purpose: To quantitatively predict the impact of cardiopulmonary dose on overall survival (OS) after radiotherapy for locally advanced non–small cell lung cancer. Experimental Design: We used the NRG Oncology/RTOG 0617 dataset. The model building procedure was preregistered on a public website. Patients were split between a training and a set-aside validation subset (N = 306/131). The 191 candidate variables covered disease, patient, treatment, and dose-volume characteristics from multiple cardiopulmonary substructures (atria, lung, pericardium, and ventricles), including the minimum dose to the hottest x% volume (Dx%[Gy]), mean dose of the hottest x% (MOHx%[Gy]), and minimum, mean (Mean[Gy]), and maximum dose. The model building was based on Cox regression and given 191 candidate variables; a Bonferroni-corrected P value threshold of 0.0003 was used to identify predictors. To reduce overreliance on the most highly correlated variables, stepwise multivariable analysis (MVA) was repeated on 1000 bootstrapped replicates. Multivariate sets selected in ≥10% of replicates were fit to the training subset and then averaged to generate a final model. In the validation subset, discrimination was assessed using Harrell c-index, and calibration was tested using risk group stratification. Results: Four MVA models were identified on bootstrap. The averaged model included atria D45%[Gy], lung Mean[Gy], pericardium MOH55%[Gy], and ventricles MOH5%[Gy]. This model had excellent performance predicting OS in the validation subset (c = 0.89). Conclusions: The risk of death due to cardiopulmonary irradiation was accurately modeled, as demonstrated by predictions on the validation subset, and provides guidance on the delivery of safe thoracic radiotherapy.

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Tài liệu tham khảo

Bradley, 2015, Standard-dose versus high-dose conformal radiotherapy with concurrent and consolidation carboplatin plus paclitaxel with or without cetuximab for patients with stage IIIA or IIIB non-small-cell lung cancer (RTOG 0617): a randomised, two-by-two factorial phase 3 study, Lancet Oncol, 16, 187, 10.1016/S1470-2045(14)71207-0

Antonia, 2017, Durvulumab after chemoradiotherapy in stage III non-small cell lung cancer, N Engl J Med, 377, 1919, 10.1056/NEJMoa1709937

Tucker, 2016, Impact of heart and lung dose on early survival in patients with non-small cell lung cancer treated with chemoradiation, Radiother Oncol, 119, 495, 10.1016/j.radonc.2016.04.025

Stam, 2017, Heart dose associated with overall survival in locally advanced NSCLC patients treated with hypofractionated chemoradiotherapy, Radiother Oncol, 125, 62, 10.1016/j.radonc.2017.09.004

McWilliam, 2017, Radiation dose to heart base linked with poorer survival in lung cancer patients, Eur J Cancer, 85, 106, 10.1016/j.ejca.2017.07.053

Vivekanden, 2017, The impact of cardiac radiation dosimetry on survival after radiation therapy for non-small cell lung cancer, Int J Radiat Oncol Biol Phys, 99, 51, 10.1016/j.ijrobp.2017.04.026

Contreras, 2018, Cardiac dose is associated with immunosuppression and poor survival in locally advanced non-small cell lung cancer, Radiother Oncol, 128, 498, 10.1016/j.radonc.2018.05.017

Speirs, 2017, Heart dose in an independent dosimetric predictor of overall survival in locally advanced non-small cell lung cancer, J Thorac Oncol, 12, 293, 10.1016/j.jtho.2016.09.134

Deasy, 2010, Improving normal tissue complication probability models: the need to adopt a “data-pooling” culture, Int J Radiat Oncol Biol Phys, 76, 151, 10.1016/j.ijrobp.2009.06.094

Thor, The role of heart-related dose-volume metrics on overall survival in the RTOG 0617 clinical trial, 10.17605/OSF.IO/HZSVA

Wheatley, 2014, Defining a novel cardiac contouring atlas for NSCLC using cadaveric anatomy, Int J Radiat Oncol Biol Phys, 90, 658, 10.1016/j.ijrobp.2014.05.1943

El Naqa, 2006, Dose response explorer: an integrated open-source tool for exploring and modelling radiotherapy dose-volume outcome relationships, Phys Med Biol, 51, 5719, 10.1088/0031-9155/51/22/001

Mayo, 2018, American Association of Physicists in Medicine Task Group 263: standardizing nomenclatures in radiation oncology, Int J Radiat Oncol Biol Phys, 100, 1057, 10.1016/j.ijrobp.2017.12.013

Royston, 2013, External validation of a Cox prognostic model: principles and methods, BMC Med Res Methodol, 33, 1

Moons, 2015, Transparent reporting of a multivariate prediction model for individual prognosis or diagnosis (TRIPOD): explanation and elaboration, Ann Intern Med, 162, 1, 10.7326/M14-0698

Zhang, 1999, Developing robust non-linear models through bootstrap aggregated neural networks, Neurocomputing, 25, 93, 10.1016/S0925-2312(99)00054-5

Bradley, 2020, Long-term of NRG Oncology RTOG 0617: standard- versus high-dose chemoradiotherapy with or without cetuximab for unresectable stage III non-small cell lung cancer, J Clin Oncol, 38, 706, 10.1200/JCO.19.01162

Darby, 2013, Risk of ischemic heart disease in women after radiotherapy for breast cancer, N Engl J Med, 368, 987, 10.1056/NEJMoa1209825

van Nimwegen, 2016, Radiation dose-response relationship for risk of coronary heart disease in survivors of Hodgkin lymphoma, J Clin Oncol, 34, 235, 10.1200/JCO.2015.63.4444

Dess, 2017, Cardiac events after radiation therapy: combined analysis of prospective multicenter trials for locally advanced non- small-cell lung cancer, J Clin Oncol, 35, 1395, 10.1200/JCO.2016.71.6142

Wang, 2017, Cardiac toxicity after radiotherapy for stage III non-small-cell lung cancer: pooled analysis of dose-escalation trials delivering 70 to 90 Gy, J Clin Oncol, 35, 1387, 10.1200/JCO.2016.70.0229

Thor, 2020, Are unsatisfactory outcomes after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer due to a treatment-related immunosuppression, Radiother Oncol, 143, 51, 10.1016/j.radonc.2019.07.016

Chun, 2017, Impact of intensity-modulated radiation therapy technique for locally advanced non-small-cell lung cancer: a secondary analysis of the NRG Oncology RTOG 0617 randomized clinical trial, J Clin Oncol, 35, 56, 10.1200/JCO.2016.69.1378

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Clinical Cancer Research

Tập 26 Số 17

4643-4650

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