Modeling the risk of radiation-induced lung fibrosis: Irradiated heart tissue is as important as irradiated lung.
OBJECTIVE
We used normal tissue complication probability (NTCP) modeling to explore the impact of heart irradiation on radiation-induced lung fibrosis (RILF).


METHODS
We retrospectively reviewed for RILF 148 consecutive Hodgkin lymphoma (HL) patients treated with sequential chemo-radiotherapy (CHT-RT). Left, right, total lung and heart dose-volume and dose-mass parameters along with clinical, disease and treatment-related characteristics were analyzed. NTCP modeling by multivariate logistic regression analysis using bootstrapping was performed. Models were evaluated by Spearman Rs coefficient and ROC area.


RESULTS
At a median time of 13months, 18 out of 115 analyzable patients (15.6%) developed RILF after treatment. A three-variable predictive model resulted to be optimal for RILF. The two models most frequently selected by bootstrap included increasing age and mass of heart receiving >30Gy as common predictors, in combination with left lung V5 (Rs=0.35, AUC=0.78), or alternatively, the lungs near maximum dose D2% (Rs=0.38, AUC=0.80).


CONCLUSIONS
CHT-RT may cause lung injury in a small, but significant fraction of HL patients. Our results suggest that aging along with both heart and lung irradiation plays a fundamental role in the risk of developing RILF.
Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy. Electronic address: laura.cella@cnr.it.
Laura
L
Cella
Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy.
Vittoria
V
D'Avino
Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy.
Giuseppe
G
Palma
Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy; Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Italy.
Manuel
M
Conson
Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy.
Raffaele
R
Liuzzi
Department of Clinical Medicine and Surgery, Federico II University School of Medicine, Naples, Italy.
Marco
M
Picardi
Department of Health Physics, S. Camillo-Forlanini Hospital, Rome, Italy.
Maria Cristina
MC
Pressello
Department of Radiation Oncology, S. Camillo-Forlanini Hospital, Rome, Italy.
Genoveva Ionela
GI
Boboc
Department of Hematology, S. Camillo-Forlanini Hospital, Rome, Italy.
Roberta
R
Battistini
Department of Radiation Oncology, S. Camillo-Forlanini Hospital, Rome, Italy.
Vittorio
V
Donato
Institute of Biostructure and Bioimaging, National Research Council (CNR), Naples, Italy; Department of Advanced Biomedical Sciences, Federico II University School of Medicine, Naples, Italy.
Roberto
R
Pacelli
D000293:Adolescent; D000328:Adult; D000368:Aged; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006321:Heart / Q000528:radiation effects*; D006689:Hodgkin Disease / Q000188:drug therapy / Q000532:radiotherapy*; D006801:Humans; D016015:Logistic Models; D008168:Lung; D008175:Lung Neoplasms / Q000188:drug therapy / Q000532:radiotherapy*; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D017564:Radiation Pneumonitis / Q000209:etiology*; D012189:Retrospective Studies; D012306:Risk; D055815:Young Adult
Bootstrap resampling; Dose–mass histogram; Heart; Hodgkin lymphoma; NTCP; Radiation-induced lung fibrosis