Loss of lung function after chemo-radiotherapy for NSCLC measured by perfusion SPECT/CT: Correlation with radiation dose and clinical morbidity

Abstract

AbstrActbackground. The purpose of the study was to assess dose and time dependence of radiotherapy (RT)-induced changes in regional lung function measured with single photon emission computed tomography (SPECT) of the lung and relate these changes to the symptomatic endpoint of radiation pneumonitis (RP) in patients treated for non-small cell lung cancer (NSCLC). Material and methods. NSCLC patients scheduled to receive curative RT of minimum 60 Gy were included prospectively in the study. Lung perfusion SPECT/CT was performed before and three months after RT. Reconstructed SPECT/CT data were registered to treatment planning CT. Dose to the lung was segmented into regions corresponding to 0-5, 6-20, 21-40, 41-60 and  60 Gy. Changes (%) in regional lung perfusion before and after RT were correlated with regional dose and symptomatic RP (CTC grade 2-5) outcome. results. A total of 58 patients were included, of which 45 had three-month follow-up SPECT/CT scans. Analysis showed a statistically significant dose-dependent reduction in regional perfusion at three-month follow-up. The largest population composite perfusion loss was in 41-60 Gy (42.2%) and  60 Gy (41.7%) dose bins. Lung regions receiving low dose of 0-5 Gy and 6-20 Gy had corresponding perfusion increase (-7.2% and -6.1%, respectively). Regional perfusion reduction was different in patients with and without RP with the largest difference in 21-40 Gy bin (p  0.02), while for other bins the difference did not reach statistical significance. The risk of symptomatic RP was higher for the patients with perfusion reduction after RT (p  0.02), with the relative risk estimate of 3.6 (95% CI 1.1-12). conclusion. Perfusion lung function changes in a dose-dependent manner after RT. The severity of radiation-induced lung symptoms is significantly correlated with SPECT perfusion changes. Perfusion reduction early after RT is associated with a high risk of later development of symptomatic RP.

Framework for radiation pneumonitis risk stratification based on anatomic and perfused lung dosimetry

“…A relationship likely exists for pre-treatment parameters and post-treatment changes; as in, high radiation dose to perfused lung will likely lead to greater reductions in lung perfusion post-treatment. This is consistent with findings from Farr et al, who found a greater risk of pneumonitis in patients who saw a greater reduction in perfusion [24]. If pre-treatment scans can be used to predict future development of pneumonitis, then treatment can potentially be adjusted to minimize risk of pulmonary toxicity.…”

“…Farr et al noted a higher risk of symptomatic pneumonitis in those patients who had a reduction in perfusion at 3 months post-radiotherapy compared to patients who did not, with a relative risk estimate of 3.6 [24]. Although both perfusion and ventilation changes can be seen after treatment, ventilation metrics may not be as sensitive to radiation as perfusion metrics, since physiologically, the lungs can vasoconstrict to reduce blood flow to unventilated areas, but it is more difficult to constrict airways to reduce ventilation to un-perfused areas [25].…”

Using 4DCT‐ventilation to characterize lung function changes for pediatric patients getting thoracic radiotherapy

“…Two of the patients demonstrated a global dose–response, one patient did not show any decline in spatial function, and one patient showed both a global and dose‐dependent dose–response (greater ventilation reduction with increasing dose). There have been several spatial lung function dose–response studies in the adult literature 4, 17, 18, 19, 20, 21, 22. In general, the pediatric data we present echo the adult literature, in that the lung functional response can be complex, as the radiation damage is juxtaposed with potential improvement from treatment of the lung disease.…”

“…There are several possible explanations for the mixed results. While adult studies generally report an overall dose–response, the changes in the 0–20 Gy dose range have either been negative or inconclusive 4, 17, 18, 19, 20, 21, 22. One possibility is that we were not able to observe an intrapatient dose–response for three patients because the lung doses delivered in our study population did not exceed 20 Gy.…”

Sparing healthy lung by focusing the radiation beam flow onto the emphysematous regions in the treatment of lung cancer

“…For advanced‐stage inoperable LC, conventionally fractionated radiation therapy (RT) with chemotherapy is considered standard of care . Several studies have investigated the effects of RT on lung function . It appears that expected pulmonary toxicity could lead to severe complications, particularly in LC, where patients often already have reduced lung function.…”