MA06.02 Impact of Heart and Lung Radiation Dose and Lymphopenia on Non-Small Cell Lung Cancer Outcomes

Abstract

Lymphocytopenia may adversely affect survival. This effect has been hypothesised to be linked to heart and lung radiation and associated circulating immune cell dose. In this large single centre study of non-small-cell lung cancer (NSCLC) patients treated with radical chemo-radiotherapy (CRT), we assess the impact of lymphocytopenia in relation to heart and lung dose on survival and tumour control. We retrospectively analysed all NSCLC patients treated with CRT from January 2018 to December 2020. Patient, tumour and treatment characteristics, mean heart dose (MHD), mean lung dose (MLD) and relapse patterns were collected. Minimum lymphocyte count identified during and within 6 months of radiotherapy was classified ‘lymphocyte nadir’ and graded using CTCAEv5. EDIC, an estimate of effective radiation dose to circulating immune cells, was calculated based on Jin et al’s model. EDIC = (0.12xMLD) + (0.08xMHD) + (0.45+0.35x0.85x(n/45)ˆ0.5)) x (ITD/62x10ˆ3) integral body dose (ITD), fractions (n) Progression free survival (PFS) and overall survival (OS) were calculated from start of treatment and associations between variables assessed using Cox regression models. 150 of 164 patients treated with CRT had lymphocyte data. All patients received radical doses of radiotherapy with intensity-modulated radiation therapy and platinum doublet chemotherapy. 25 had adjuvant Durvalumab. Patients with ≥grade 2 lymphocytopenia at nadir (≥G2LN) had significantly worse PFS (HR=1.53, p<0.05) and OS (HR 1.69, p<0.05) than <grade 2 lymphocytopenia at nadir (<G2LN). Median OS was 26.5 and 35.1 months respectively. Patient and treatment characteristics are summarised in table 1. There was no significant difference in OS between sequential and concurrent CRT. Mean MHD and MLD were higher in patients with ≥G2LN compared to <G2LN (10.7Gy vs 7.8Gy and 13.4Gy vs 11Gy respectively) though not significantly. Larger planning target volume (PTV) was significantly associated with worse OS (HR=1.002, p<0.001) and correlated with lymphocyte nadir (Pearson r=-0.40, p<0.001). 111 patients had EDIC measures. EDIC negatively correlated with lymphocyte nadir (Pearson r=-0.237, p=0.017). Median EDIC was 2.38. EDIC ≥2.38 was associated with worse OS compared to <2.38 (19.5 vs 36.9 months respectively) (HR=1.75, p=0.067). Larger PTVs result in higher MHD, MLD and effective radiation dose to circulating immune cells, resulting in lower lymphocyte nadir which is associated with poorer outcomes. Lymphocyte nadir appears to be a surrogate for survival; we recommend closer surveillance of patients with ≥G2LN, reducing MHD and MLD to as low as possible and considering pneumocystis-jiroveci-pneumonia (PJP) prophylaxis. The additional impact of adjuvant immunotherapy would be interesting to assess.