## 4 Discussion  
An example of application of radiological parameters to discriminate pathophysiological features is the DTI in the brain neoplasm, where different ADCmean values are related to different histologies [16,17]. In the same way, the pulmonary function test is well described as a useful tool to assess lung functionality and can potentially predict the risk of RIP in candidates to curative treatment for LA-NSCLC [8]. The SPECT-optimized plan was developed by giving higher priority to the isoROI 80% corresponding to very small lung volumes. This procedure allowed us to maintain the same dose volume histogram (DVH) between the standard and SPECT optimized plan in term of target coverage. At the same time, the SPECT-optimized RT plan allowed us to better satisfy the selected dose-volume parameters such as V5, V20 and MLD. This optimization also allowed us to obtain a clear advantage for isoROI 60%, while it was just marginally achieved for isoROI 40%. This suggests that the optimization effort profused on small lung volumes (isoROI 80%) could improve dose distribution even on larger lung volumes.  
Figure 3: (a) Standard RT plan and (b) SPECT/CT-optimized RT plan.  
\begin{table}
\begin{tabular}{c|c c c} \hline
**IsoROI \(\geq\) 20\% Max Perfusion** & **Plane 1** & **Plane 2** & \(p\) \\ \hline
**Mean dose cumulative lung minus PTV** & 14 & 14 & ns \\ \hline
**V20** & 20 & 20 & ns \\ \hline
**V5** & 54 & 57 & ns \\ \hline
**IsoROI\(>\) 40\% max perfusion** & **Plane 1** & **Plane 2** & \(p\) \\ \hline
**Mean dose cumulative lung minus PTV** & 14 & 13 & 0.042 \\ \hline
**V20** & 20 & 19 & ns \\ \hline
**V5** & 56 & 56 & ns \\ \hline
**IsoROI\(>\) 60\% max perfusion** & **Plane 1** & **Plane 2** & \(p\) \\ \hline
**Mean dose cumulative lung minus PTV** & 14 & 11 & 0.025 \\ \hline
**V20** & 23 & 16 & ns (0.05) \\ \hline
**V5** & 57 & 54 & 0.023 \\ \hline \end{tabular}
\end{table}
Table 3: Results of the DVH analysis of the isoROIs of plane 1 and plane 2.  
Pulmonary perfusion assessment could also be particularly relevant for RIP damage. Preserving lung parenchyma with optimal perfusion is likely to reduce the resulting vascular damage and the risk of pulmonary toxicity [18].  
The main limits of this study are its retrospective nature, the limited number of cases and the lack of correlation between dosimetric data and clinical outcomes. Nonetheless, results of this pilot analysis are promising in terms of possibility to spare the better perfused lung volumes, with the chance to reduce the risk of RIP in functional lung. This preliminary hypothesis-generating experience warrants the evaluation of SPECT-guided radiotherapy in prospective and larger series to confirm the real clinical impact of integrating SPECT information into the treatment planning workflow to better avoid severe pulmonary toxicity.  
Conceptualization: P.B. and J.L; methodology: A.B. and J.L; software, C.T.; validation: S.L. and F.V.; formal analysis: G.V. and N.S.; investigation: J.I.; resources: G.F.; data curation: S.L.M. and A.G.; writing--original draft preparation: J.I. and N.S.; writing--review and editing: J.L. and P.B.; visualization: P.B. and A.B.; pervision: M.B.d.M.e.B.; project administration: P.B. All authors have read and agreed to the published version of the manuscript.  
Authors declare that no funds, grants or other support were received during the preparation of this manuscript.  
This is a retrospective study, based on anonymized data, no ethical approval and no informed consent regarding participation or publishing are required by the involved center.  
Absence of any kind of any active or previous conflict of interest: no relevant financial or non-financial interests to disclose.