Clinical Significance of Total Radiation Dose for Patients With Treatment Delays in Stage III Non-Small Cell Lung Cancer.

Abstract

PURPOSE/OBJECTIVE(S)\nDelays during definitive radiation treatment are not uncommon, as highlighted by the ongoing COVID-19 pandemic, and are associated with worse survival. We aim to utilize the National Cancer Database (NCDB) to determine whether prolonged chemoradiation (CRT) treatment time in stage III non-small cell lung cancer (NSCLC) can be compensated for by an increase in total radiation dose.\n\n\nMATERIALS/METHODS\nWe identified 26,101 patients who were treated curatively with CRT using standard doses (59.4-66.6 Gy) and fractionation for stage III NSCLC between 2004-2017. Treatments were classified as non-prolonged or prolonged. The total number of days allowed for non-prolonged treatment for each dose/fractionation was calculated by adding number of fractions, weekend days (to accommodate any weekday start), and 2 additional days. Any treatment exceeding this number of days was prolonged. Multivariable Cox proportional regression was used to assess the association between specific doses and treatment durations and OS while adjusting for age, gender, race, comorbidity score, insurance status, facility type, urban/rural location, education, clinical T and N category.\n\n\nRESULTS\nOf 26,101 patients, 57% were male and the median age was 67. The most common T and N stage were T2 (31%) and N2 (64%), respectively. The majority of patients (62%) did not have prolonged treatment. For those who had prolonged treatment, the median prolongation was 4 days and survival was worse (HR 1.256, P\u202f=\u202f< 0.0001). Comparison of non-prolonged and prolonged treatment was then limited to two dose levels: 60 Gy and 66 Gy, both delivered in 2 Gy fractions (13,189 patients). Both doses resulted in similar survival for non-prolonged treatment (HR for 60 Gy non-prolonged: reference; HR for 66 Gy non-prolonged: 1.01, P\u202f=\u202f0.633) and worse survival if treatment was prolonged (HR for 60 Gy prolonged: 1.294, P\u202f=\u202f< 0.0001; HR for 66 Gy prolonged: 1.216, P\u202f=\u202f< 0.0001). Direct comparison of the prolonged groups for 60 Gy and 66 Gy is tabulated below. For prolongation of 1-3 days, 66 Gy and 60 Gy were equivalent. If treatment was prolonged for 4 days or longer, survival was improved for higher total radiation dose.\n\n\nCONCLUSION\nProlonged CRT in stage III NSCLC is associated with worse survival. Alteration of total dose should be considered for prolonged treatment time, especially as the number of missed days increases.