Session Item

To date no consistent dosimetric parameters related to overall survival (OS) and cardiac toxicity in early stage (ES) and locally advanced (LA) NSCLC patients have been identified. The aim of this prospective study is to investigate for any existing correlation between the dose delivered to the heart and to cardiac and vascular structures and OS, non-tumor-related survival and the development of cardiac toxicity, in ES-NSCLC and LA-NSCLC patients treated with definitive RT.

Patients with PS ECOG score 0-1 and no previous RT treatment to the mediastinum were included. Details on pre-existing cardiovascular risk factors and comorbidities, ongoing drug therapies and lung function tests were collected at baseline. The Charlson Comorbidity Index (CCI) was calculated at the time of the first clinical evaluation. Cardiac substructures (valves, chambers and coronary arteries) were prospectively contoured in order to collect dosimetric data. Cardiac toxicity events were evaluated with the CTCAE 5.0 grading. OS was estimated with the Kaplan-Meier method from the date of the last of RT session.

From March 2019 to September 2021, 115 patients were enrolled. Of these, 69 received Stereotactic Ablative RT (SABR) with a “risk adapted” fractionation schedule (1-8 fractions); 46 LA-NSCLC patients were treated with combined chemo-radiotherapy, with doses of 54-60 Gy (2 Gy/fr). Overall, 14 patients (15%) developed at least one event of cardiac toxicity during the observation period and 26 patients were dead (16 ES-NSCLC and 10 LA-NSCLC) at the time of this analysis. With a median follow up of 14 months, we observed that patients who developed cardiac toxicity had a higher risk of death at 1 year compared to the others (1yOS: 67.5 % vs 86.5 %, p= 0.03). Moreover, the presence of pre-existing cardiac diseases had a negative impact on OS at 1 year (70% vs 84.7% p=0.034) (Figure 1). Hazard ratios for pre-existing cardiac diseases and cardiac toxicity were 2.33 [IC95%=1.036-5.253] and 2.71 [IC95%=1.044-7.05], respectively. No correlation between the CCI (0-4 vs ≥5) and OS was revealed (p= 0.77) on the overall population. The analysis of dosimetric parameters was carried out separately for the two groups. Despite the limitations due to our modest sample size, heart V40 and V50 were associated with cardiac toxicity in the LA-NSCLC group, with an OR of 1.46 (p=0.043) and 1.61 (p=0.05), respectively. To date no correlations were found in the ES-NSCLC group.

According to our results, pre-existing heart comorbidities and the onset of cardiac toxicity predict a higher risk of mortality in NSCLC patients treated with RT. Therefore, the risk of developing cardiac toxicity must be carefully considered in all patients. Preliminary dosimetric data suggest a possible correlation between heart dosimetry and the development of RT related cardiac toxicity, but longer follow up periods are required to confirm these findings.