Low Dose Radiotherapy in the Management of COVID-19 Pneumonia (LOWRAD-Cov19).

Abstract

Purpose/Objective(s) To evaluate the safety and efficacy of Low-Dose Radiation (LD-RT) to treat COVID-19 pneumonia. Materials/Methods We conducted a prospective phase I-II trial enrolling patients ≥ 50 years-old, COVID-19 positive, with lung involvement at imaging study and oxygen requirement. Patients received 100 cGy to total lungs in a single fraction. Dose planning goals were PTV95 > 80% with Dmax < 115%. Primary outcome was radiological response assessed as severity and extension scores at days 0, +3 and +7. Secondary outcomes were toxicity (CTCAE v5.0), days of hospitalization, changes in inflammatory blood parameters (ferritin, lymphocytes, C-reactive protein, d-dimer and LDH) and SatO2/ FiO2 index (SAFI) at +3 and +7 (normal SAFI > 315, mild respiratory failure < 300, and severe < 200). Descriptive analyses were summarized as means with standard deviation (SD) and medians with interquartile ranges (IQR). A Wilcoxon sign rank test for paired data was used to assess the CT scores and Chi Square was used to assess for comparison of categorical variables. Results Forty-one patients were included. Three patients died < 72h after LD-RT and were excluded from the analysis. Median age was 71 (IQR 60-84). Eighteen patients (47%) received previously any anti-COVID treatment (tocilizumab, lopinavir/ritonavir, remdesivir) and thirty-two patients (84%) received steroids (GC) during LD-RT. Extension score improved significantly ( P = 0.02) on day +7; severity score was stable or slightly decreased ( P = 0.1). Median SAFI on day 0 was 147 (IQR 118-264), 230 (IQR 120-343) on day +3 and 293 (IQR 121-353) on day +7 ( P < 0.01). SAFI improvement was associated with overall survival ( P = 0.01). Significant decrease was found in C-reactive protein on day +7 ( P = 0.02) and in lymphocytes counts on day +3 and +7 ( P = 0.02). Median time to receive RT from the date of admission was 19 days (ranging 2-87). Median number of days in hospital after RT was 11 (4-78) and overall was 37 days (range 11-155). With a median follow-up of 67 days after LD-RT, 24 (63%) patients were discharged, twelve (32%) died and two (5%) are still inpatients. Conclusion Our preliminary results show that LD-RT was feasible and well-tolerated treatment, with potential clinical improvement. Randomized trials are needed to establish whether LD-RT improves severe pneumonia.