Proton and photon radiotherapy in stage III NSCLC: effects on hematological toxicity and adjuvant immune therapy

BACKGROUND AND PURPOSE: Concurrent chemo-radiotherapy (CCRT) followed by adjuvant durvalumab is standard-of-care for fit patients with unresectable stage III NSCLC. Intensity modulated proton therapy (IMPT) results in different doses to organs than intensity modulated photon therapy (IMRT). We investigated whether IMPT compared to IMRT reduce hematological toxicity and whether it affects durvalumab treatment. MATERIALS AND METHODS: Prospectively collected series of consecutive patients with stage III NSCLC receiving CCRT between 06.16 and 12.22 (staged with FDG-PET-CT and brain imaging) were retrospectively analyzed. The primary endpoint was the incidence of lymphopenia grade =3 in IMPT vs IMRT treated patients. RESULTS: 271 patients were enrolled (IMPT: n=71, IMRT: n=200) in four centers. All patients received platinum-based chemotherapy. Median age: 66 years, 58% were male, 36% had squamous NSCLC. The incidence of lymphopenia grade =3 during CCRT was 67% and 47% in the IMRT and IMPT group, respectively (OR 2.2, 95% CI: 1.0-4.9, P=0.03). The incidence of anemia grade =3 during CCRT was 26% and 9% in the IMRT and IMPT group respectively (OR=4.9, 95% CI: 1.9-12.6, P=0.001). IMPT was associated with a lower rate of Performance Status (PS)=2 at day 21 and 42 after CCRT (13% vs. 26%, P=0.04, and 24% vs. 39%, P=0.02). Patients treated with IMPT had a higher probability of receiving adjuvant durvalumab (74% vs. 52%, OR 0.35, 95% CI: 0.16-0.79, P=0.01). CONCLUSION: IMPT was associated with a lower incidence of severe lymphopenia and anemia, better PS after CCRT and a higher probability of receiving adjuvant durvalumab.