Relationship Between Prior Radiotherapy and Checkpoint-Inhibitor Pneumonitis in Patients With Advanced Non–Small-Cell Lung Cancer

Khinh Voong, Sarah Z. Hazell, Wei Fu, Chen Hu, Cheng Lin, Kai Ding, Karthik Suresh, Jonathan Hayman, Russell Hales, Salem Alfaifi, Kristen Marrone, Benjamin Levy, Christine Hann, David S Ettinger, Josephine Feliciano, Valerie Peterson, Ronan J. Kelly, Julie Brahmer, Patrick Forde, Jarushka Naidoo

Research output: Contribution to journalArticle

Abstract

Purpose: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR)pneumonitis in non–small-cell lung cancer (NSCLC)patients treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). Patients and Methods: Between June 2011 and July 2017, NSCLC patients treated with anti–PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. Results: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3)months and median age 66 (range, 39-91)years; 54% (n = 102)were male; and 42% (n = 79)had stage I-III NSCLC at initial diagnosis. Patients received anti–PD-1/PD-L1 monotherapy (n = 127, 68%)or PD-1/PD-L1-based combinations (n = 61, 32%). In the entire cohort, 70% (132/188)received any RT, 53% (100/188)chest RT, and 37% (70/188)curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P =.051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. Conclusion: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti–PD-1/PD-L1 agents.

Original languageEnglish (US)
JournalClinical Lung Cancer
DOIs
StatePublished - Jan 1 2019

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Non-Small Cell Lung Carcinoma
Pneumonia
Radiotherapy
Thorax
Ligands
Nonparametric Statistics
Tertiary Healthcare
Glass
Cell Death

Keywords

  • Anti–PD-1/PD-L1 therapy
  • Nivolumab
  • Pembrolizumab
  • Pneumonitis
  • Radiation

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

@article{f6240614f42c4dd59b708d1b648ed8df,
title = "Relationship Between Prior Radiotherapy and Checkpoint-Inhibitor Pneumonitis in Patients With Advanced Non–Small-Cell Lung Cancer",
abstract = "Purpose: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR)pneumonitis in non–small-cell lung cancer (NSCLC)patients treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). Patients and Methods: Between June 2011 and July 2017, NSCLC patients treated with anti–PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. Results: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3)months and median age 66 (range, 39-91)years; 54{\%} (n = 102)were male; and 42{\%} (n = 79)had stage I-III NSCLC at initial diagnosis. Patients received anti–PD-1/PD-L1 monotherapy (n = 127, 68{\%})or PD-1/PD-L1-based combinations (n = 61, 32{\%}). In the entire cohort, 70{\%} (132/188)received any RT, 53{\%} (100/188)chest RT, and 37{\%} (70/188)curative-intent chest RT. Any grade IR pneumonitis occurred in 19{\%} (36/188; 95{\%} confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89{\%}, vs. 2/19, 11{\%}; P =.051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. Conclusion: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti–PD-1/PD-L1 agents.",
keywords = "Anti–PD-1/PD-L1 therapy, Nivolumab, Pembrolizumab, Pneumonitis, Radiation",
author = "Khinh Voong and Hazell, {Sarah Z.} and Wei Fu and Chen Hu and Cheng Lin and Kai Ding and Karthik Suresh and Jonathan Hayman and Russell Hales and Salem Alfaifi and Kristen Marrone and Benjamin Levy and Christine Hann and Ettinger, {David S} and Josephine Feliciano and Valerie Peterson and Kelly, {Ronan J.} and Julie Brahmer and Patrick Forde and Jarushka Naidoo",
year = "2019",
month = "1",
day = "1",
doi = "10.1016/j.cllc.2019.02.018",
language = "English (US)",
journal = "Clinical Lung Cancer",
issn = "1525-7304",
publisher = "Elsevier",

}

TY - JOUR

T1 - Relationship Between Prior Radiotherapy and Checkpoint-Inhibitor Pneumonitis in Patients With Advanced Non–Small-Cell Lung Cancer

AU - Voong, Khinh

AU - Hazell, Sarah Z.

AU - Fu, Wei

AU - Hu, Chen

AU - Lin, Cheng

AU - Ding, Kai

AU - Suresh, Karthik

AU - Hayman, Jonathan

AU - Hales, Russell

AU - Alfaifi, Salem

AU - Marrone, Kristen

AU - Levy, Benjamin

AU - Hann, Christine

AU - Ettinger, David S

AU - Feliciano, Josephine

AU - Peterson, Valerie

AU - Kelly, Ronan J.

AU - Brahmer, Julie

AU - Forde, Patrick

AU - Naidoo, Jarushka

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Purpose: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR)pneumonitis in non–small-cell lung cancer (NSCLC)patients treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). Patients and Methods: Between June 2011 and July 2017, NSCLC patients treated with anti–PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. Results: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3)months and median age 66 (range, 39-91)years; 54% (n = 102)were male; and 42% (n = 79)had stage I-III NSCLC at initial diagnosis. Patients received anti–PD-1/PD-L1 monotherapy (n = 127, 68%)or PD-1/PD-L1-based combinations (n = 61, 32%). In the entire cohort, 70% (132/188)received any RT, 53% (100/188)chest RT, and 37% (70/188)curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P =.051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. Conclusion: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti–PD-1/PD-L1 agents.

AB - Purpose: To investigate the relationship between radiotherapy (RT), in particular chest RT, and development of immune-related (IR)pneumonitis in non–small-cell lung cancer (NSCLC)patients treated with anti–programmed cell death 1 (PD-1)/programmed death ligand 1 (PD-L1). Patients and Methods: Between June 2011 and July 2017, NSCLC patients treated with anti–PD-1/PD-L1 at a tertiary-care academic cancer center were identified. Patient, treatment, prior RT (intent, technique, timing, courses), and IR pneumonitis details were collected. Treating investigators diagnosed IR pneumonitis clinically. Diagnostic IR pneumonitis scans were overlaid with available chest RT plans to describe IR pneumonitis in relation to prior chest RT. We evaluated associations between patient, treatment, RT details, and development of IR pneumonitis by Fisher exact and Wilcoxon rank-sum tests. Results: Of the 188 NSCLC patients we identified, median follow-up was 6.78 (range, 0.30-79.3)months and median age 66 (range, 39-91)years; 54% (n = 102)were male; and 42% (n = 79)had stage I-III NSCLC at initial diagnosis. Patients received anti–PD-1/PD-L1 monotherapy (n = 127, 68%)or PD-1/PD-L1-based combinations (n = 61, 32%). In the entire cohort, 70% (132/188)received any RT, 53% (100/188)chest RT, and 37% (70/188)curative-intent chest RT. Any grade IR pneumonitis occurred in 19% (36/188; 95% confidence interval, 13.8-25.6). Of those who developed IR pneumonitis and received chest RT (n = 19), patients were more likely to have received curative-intent versus palliative-intent chest RT (17/19, 89%, vs. 2/19, 11%; P =.051). Predominant IR pneumonitis appearances were ground-glass opacities outside high-dose chest RT regions. Conclusion: No RT parameter was significantly associated with IR pneumonitis. On subset analysis of patients who developed IR pneumonitis and who had received prior chest RT, IR pneumonitis was more common in patients who received curative-intent chest RT. Attention should be paid to NSCLC patients receiving curative-intent RT followed by anti–PD-1/PD-L1 agents.

KW - Anti–PD-1/PD-L1 therapy

KW - Nivolumab

KW - Pembrolizumab

KW - Pneumonitis

KW - Radiation

UR - http://www.scopus.com/inward/record.url?scp=85064644650&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85064644650&partnerID=8YFLogxK

U2 - 10.1016/j.cllc.2019.02.018

DO - 10.1016/j.cllc.2019.02.018

M3 - Article

C2 - 31031204

AN - SCOPUS:85064644650

JO - Clinical Lung Cancer

JF - Clinical Lung Cancer

SN - 1525-7304

ER -