Cardiac events after radiation therapy

Combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer

Robert T. Dess, Yilun Sun, Martha M. Matuszak, Grace Sun, Payal D. Soni, Latifa Bazzi, Venkatesh L. Murthy, Jason W.D. Hearn, Feng Ming Kong, Gregory P. Kalemkerian, James A. Hayman, Randall K. Ten Haken, Theodore S. Lawrence, Matthew J. Schipper, Shruti Jolly

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Purpose: Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials: Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results: In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had preexisting cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion: The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.

Original languageEnglish (US)
Pages (from-to)1395-1402
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number13
DOIs
StatePublished - May 1 2017

Fingerprint

Non-Small Cell Lung Carcinoma
Multicenter Studies
Radiotherapy
Preexisting Condition Coverage
Disease Progression
Heart Diseases
Incidence
Radiation
Radiation Injuries
Terminology
Prescriptions
Patient Care
Drug Therapy
Survival
Wounds and Injuries
Neoplasms

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cardiac events after radiation therapy : Combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer. / Dess, Robert T.; Sun, Yilun; Matuszak, Martha M.; Sun, Grace; Soni, Payal D.; Bazzi, Latifa; Murthy, Venkatesh L.; Hearn, Jason W.D.; Kong, Feng Ming; Kalemkerian, Gregory P.; Hayman, James A.; Ten Haken, Randall K.; Lawrence, Theodore S.; Schipper, Matthew J.; Jolly, Shruti.

In: Journal of Clinical Oncology, Vol. 35, No. 13, 01.05.2017, p. 1395-1402.

Research output: Contribution to journalArticle

Dess, RT, Sun, Y, Matuszak, MM, Sun, G, Soni, PD, Bazzi, L, Murthy, VL, Hearn, JWD, Kong, FM, Kalemkerian, GP, Hayman, JA, Ten Haken, RK, Lawrence, TS, Schipper, MJ & Jolly, S 2017, 'Cardiac events after radiation therapy: Combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer', Journal of Clinical Oncology, vol. 35, no. 13, pp. 1395-1402. https://doi.org/10.1200/JCO.2016.71.6142
Dess, Robert T. ; Sun, Yilun ; Matuszak, Martha M. ; Sun, Grace ; Soni, Payal D. ; Bazzi, Latifa ; Murthy, Venkatesh L. ; Hearn, Jason W.D. ; Kong, Feng Ming ; Kalemkerian, Gregory P. ; Hayman, James A. ; Ten Haken, Randall K. ; Lawrence, Theodore S. ; Schipper, Matthew J. ; Jolly, Shruti. / Cardiac events after radiation therapy : Combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer. In: Journal of Clinical Oncology. 2017 ; Vol. 35, No. 13. pp. 1395-1402.
@article{724fb65ab81446e4b6aef98883cacf90,
title = "Cardiac events after radiation therapy: Combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer",
abstract = "Purpose: Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials: Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results: In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84{\%} received concurrent chemotherapy, and 27{\%} had preexisting cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11{\%} (95{\%} CI, 5{\%} to 16{\%}). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95{\%} CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95{\%} CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95{\%} CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95{\%} CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion: The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10{\%} among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.",
author = "Dess, {Robert T.} and Yilun Sun and Matuszak, {Martha M.} and Grace Sun and Soni, {Payal D.} and Latifa Bazzi and Murthy, {Venkatesh L.} and Hearn, {Jason W.D.} and Kong, {Feng Ming} and Kalemkerian, {Gregory P.} and Hayman, {James A.} and {Ten Haken}, {Randall K.} and Lawrence, {Theodore S.} and Schipper, {Matthew J.} and Shruti Jolly",
year = "2017",
month = "5",
day = "1",
doi = "10.1200/JCO.2016.71.6142",
language = "English (US)",
volume = "35",
pages = "1395--1402",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "13",

}

TY - JOUR

T1 - Cardiac events after radiation therapy

T2 - Combined analysis of prospective multicenter trials for locally advanced non-small-cell lung cancer

AU - Dess, Robert T.

AU - Sun, Yilun

AU - Matuszak, Martha M.

AU - Sun, Grace

AU - Soni, Payal D.

AU - Bazzi, Latifa

AU - Murthy, Venkatesh L.

AU - Hearn, Jason W.D.

AU - Kong, Feng Ming

AU - Kalemkerian, Gregory P.

AU - Hayman, James A.

AU - Ten Haken, Randall K.

AU - Lawrence, Theodore S.

AU - Schipper, Matthew J.

AU - Jolly, Shruti

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Purpose: Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials: Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results: In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had preexisting cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion: The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.

AB - Purpose: Radiation therapy is a critical component in the care of patients with non-small-cell lung cancer (NSCLC), yet cardiac injury after treatment is a significant concern. Therefore, we wished to elucidate the incidence of cardiac events and their relationship to radiation dose to the heart. Patients and Materials: Study eligibility criteria included patients with stage II to III NSCLC treated on one of four prospective radiation therapy trials at two centers from 2004 to 2013. All cardiac events were reviewed and graded per Common Terminology Criteria for Adverse Events (v4.03). The primary end point was the development of a grade ≥ 3 cardiac event. Results: In all, 125 patients met eligibility criteria; median follow-up was 51 months for surviving patients. Median prescription dose was 70 Gy, 84% received concurrent chemotherapy, and 27% had preexisting cardiac disease. Nineteen patients had a grade ≥ 3 cardiac event at a median of 11 months (interquartile range, 6 to 24 months), and 24-month cumulative incidence was 11% (95% CI, 5% to 16%). On multivariable analysis (MVA), pre-existing cardiac disease (hazard ratio [HR], 2.96; 95% CI, 1.07 to 8.21; P = .04) and mean heart dose (HR, 1.07/Gy; 95% CI, 1.02 to 1.13/Gy; P = .01) were significantly associated with grade ≥ 3 cardiac events. Analyzed as time-dependent variables on MVA analysis, both disease progression (HR, 2.15; 95% CI, 1.54 to 3.00) and grade ≥ 3 cardiac events (HR, 1.76; 95% CI, 1.04 to 2.99) were associated with decreased overall survival. However, disease progression (n = 71) was more common than grade ≥ 3 cardiac events (n = 19). Conclusion: The 24-month cumulative incidence of grade ≥ 3 cardiac events exceeded 10% among patients with locally advanced NSCLC treated with definitive radiation. Pre-existing cardiac disease and higher mean heart dose were significantly associated with higher cardiac event rates. Caution should be used with cardiac dose to minimize risk of radiation-associated injury. However, cardiac risks should be balanced against tumor control, given the unfavorable prognosis associated with disease progression.

UR - http://www.scopus.com/inward/record.url?scp=85018346472&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85018346472&partnerID=8YFLogxK

U2 - 10.1200/JCO.2016.71.6142

DO - 10.1200/JCO.2016.71.6142

M3 - Article

VL - 35

SP - 1395

EP - 1402

JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

IS - 13

ER -