ABSTRACT
BACKGROUND AND PURPOSE: To report on the anti-tumor activity of a novel combination in high-risk locally advanced head and neck squamous cell carcinoma. MATERIALS AND METHODS: At a fixed dose of 1500 mg every 28 days, anti PD-L1 Durvalumab was given concomitantly to Radiotherapy and Cetuximab starting from the first week of combined treatment, followed by adjuvant Durvalumab to a maximum of 6 months after completion of radiation. The primary endpoint of the study was 2-year progression-free survival (PFS). A safety run-in was planned. Due to regulatory issues which prevented from opening multiple centers, COVID-19 pandemic and withdrawal of Durvalumab from supporting company, the study was prematurely terminated in April 2021. RESULTS: Between July 2019 and August 2020, 9 patients were enrolled in the study. All tumors had a PD-L1 Combined Positive Score > 1. Optimal drug exposure was observed, with mean relative dose intensity of 85.5% and 87.5% for Cetuximab and Durvalumab, respectively. No radiation breaks were necessary. A grade 4 mucositis lasting for 14 days corresponded to the only dose limiting toxicity we reported. At a median follow-up of 11.5 months (IQR 7.7-16.7) all surviving patients (6 out of 9) are disease-free, with 1 and 2-year PFS rates of 77.7% and 58.3%, respectively. A selective sparing of node levels in the elective volume was performed in all cases, yielding a cumulative mean dose of 37.6 Gy (SD 8.4). CONCLUSION: Albeit limited by the small sample size, our preliminary observation of anti-tumor activity and tolerability of Durvalumab in addition to Cetuximab and radiation may warrant further investigations.
Subject(s)
Antineoplastic Combined Chemotherapy Protocols , Head and Neck Neoplasms , Squamous Cell Carcinoma of Head and Neck , Antibodies, Monoclonal/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , COVID-19 , Cetuximab/therapeutic use , Head and Neck Neoplasms/drug therapy , Humans , Pandemics , Squamous Cell Carcinoma of Head and Neck/drug therapy , Squamous Cell Carcinoma of Head and Neck/pathologyABSTRACT
BACKGROUND AND PURPOSE: COVID-19 constitutes a worldwide threat, prompting Italian Government to implement specific measures on March 8, 2020, to protect patients and health workers from disease transmission. The impact of preventive measures on daily activity of a radiotherapy facility may hamper the ability to fulfill normal workload burden. Thus, we assessed the number of delivered treatments in a specific observation period after the adoption of preventive measures (since March 11 to April 24, 2020) and compared it with the corresponding period of the year 2019. MATERIALS AND METHODS: Overall number of delivered fractions was related to actual time of platform daily activity and reported as a ratio between number of delivered fractions and activity hours (Fr/Hrs). Fr/Hrs were calculated and compared for two different periods of time, March 11-April 24, 2019 (Fr/Hrs1), and March 11-April 24, 2020 (Fr/Hrs2). RESULTS: Fr/Hrs1 and Fr/Hrs2 were 2.66 and 2.54 for year 2019 and 2020, respectively, for a Fr/Hrsratio of 1.07 (95% CI 1.03-1.12, p = 0.0005). Fr/Hrs1 was significantly higher than Fr/Hrs2 for SliR and PreciseR, with Fr/Hrsratio of 1.92 (95% CI 1.66-2.23, p < 0.0001) and 1.11 (95% CI 1.03-1.2, p = 0.003), respectively. No significant difference was reported for SynergyR and CyberknifeR with Fr/Hrsratio of 0.99 (95% CI 0.91-1.08, p = 0.8) and 0.9 (95% CI 0.77-1.06, p = 0.2), respectively. Fr/Hrs1 was significantly lower than Fr/Hrs2 for TomotherapyR, with Fr/Hrsratio of 0.88 (95% CI 0.8-0.96, p = 0.007). CONCLUSION: Preventive measures did not influence workload burden performed. Automation in treatment delivery seems to compensate effectively for health workers number reduction.