TY - JOUR
T1 - Causal relation between heart irradiation and survival of lung cancer patients after radiotherapy
AU - Brink, Carsten
AU - Bernchou, Uffe
AU - Bertelsen, Anders
AU - Hansen, Olfred
AU - Schytte, Tine
AU - Hjelmborg, Jacob V B
AU - Holloway, Lois
AU - van Herk, Marcel
AU - Johnson-Hart, Corinne
AU - Price, Gareth J
AU - Aznar, Marianne C
AU - McWilliam, Alan
AU - Faivre-Finn, Corinne
AU - Hansen, Christian R
N1 - Funding Information:
CFF and MvH are supported by the NIHR Manchester Biomedical Research Centre.
Funding Information:
CB and OH acknowledge support from AgeCare (Academy of Geriatric Cancer Research), an international research collaboration based at Odense University Hospital, Denmark.
Funding Information:
GJP is funded by Cancer Research UK through the CRUK Manchester Centre [C147/A18083] and [C147/ a25254]
Funding Information:
TS acknowledges support from Independent Research Fund Denmark.
Publisher Copyright:
© 2022 Elsevier B.V.
PY - 2022/7
Y1 - 2022/7
N2 - INTRODUCTION: In a recent study, setup uncertainties in the direction of the heart were shown to impact the overall survival of non-small cell lung cancer (NSCLC) patients after radiotherapy, indicating the causal effect between heart irradiation and survival. The current study aims to externally evaluate this observation within a patient cohort treated using daily IGRT.METHOD: NSCLC patients with locally-advanced disease and daily CBCT were included. For all treatment fractions, the distance between the isocenter and the heart was evaluated based on the clinical setup registrations. The variation in heart position between planning and treatment (DeltaDistance) was estimated from these registrations. The possible impact of DeltaDistance on survival was analysed by a multivariable Cox model of overall survival, allowing for a time-dependent impact of DeltaDistance to allow for toxicity latency.RESULTS: Daily CBCT information was available for 489 patients at Odense University Hospital. The primary Cox model contained GTV volume, patient age, performance status, and DeltaDistance. DeltaDistance significantly impacted overall survival approximately 50 months after radiotherapy. Subanalyses indicated that the observed effect is mainly present among the patients with the least clinical risk factors.CONCLUSION: Our results confirm the impact of setup variations in the direction of the heart on the survival of NSCLC patients, even within a cohort using daily CBCT setup guidance. This result indicates a causal effect between heart irradiation and survival. It will be challenging to reduce the setup uncertainty even further; thus, increased focus on dose constraints on the heart seems warranted.
AB - INTRODUCTION: In a recent study, setup uncertainties in the direction of the heart were shown to impact the overall survival of non-small cell lung cancer (NSCLC) patients after radiotherapy, indicating the causal effect between heart irradiation and survival. The current study aims to externally evaluate this observation within a patient cohort treated using daily IGRT.METHOD: NSCLC patients with locally-advanced disease and daily CBCT were included. For all treatment fractions, the distance between the isocenter and the heart was evaluated based on the clinical setup registrations. The variation in heart position between planning and treatment (DeltaDistance) was estimated from these registrations. The possible impact of DeltaDistance on survival was analysed by a multivariable Cox model of overall survival, allowing for a time-dependent impact of DeltaDistance to allow for toxicity latency.RESULTS: Daily CBCT information was available for 489 patients at Odense University Hospital. The primary Cox model contained GTV volume, patient age, performance status, and DeltaDistance. DeltaDistance significantly impacted overall survival approximately 50 months after radiotherapy. Subanalyses indicated that the observed effect is mainly present among the patients with the least clinical risk factors.CONCLUSION: Our results confirm the impact of setup variations in the direction of the heart on the survival of NSCLC patients, even within a cohort using daily CBCT setup guidance. This result indicates a causal effect between heart irradiation and survival. It will be challenging to reduce the setup uncertainty even further; thus, increased focus on dose constraints on the heart seems warranted.
KW - Carcinoma, Non-Small-Cell Lung/radiotherapy
KW - Humans
KW - Lung Neoplasms/radiotherapy
KW - Radiotherapy Dosage
KW - Radiotherapy Planning, Computer-Assisted/methods
KW - Radiotherapy Setup Errors
KW - Thorax
U2 - 10.1016/j.radonc.2022.05.002
DO - 10.1016/j.radonc.2022.05.002
M3 - Article
C2 - 35545166
SN - 0167-8140
VL - 172
SP - 126
EP - 133
JO - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
JF - Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology
ER -
