Patients
This retrospective study included 347 adult cancer patients who received radiotherapy or chemoradiotherapy at Shandong Cancer Hospital in China between July 2022 and March 2023. We excluded young patients and adult patients who underwent simple chemotherapy. The primary endpoint was discharge from the hospital based on the medical records. Based on their Omicron infection status and duration of treatment delay after the infection, patients were divided into three groups: a non-COVID-19 group (n = 108), a < 10-d COVID-19 group (n = 137), and a ≥ 10-d COVID-19 group (n = 102). The non-COVID-19 group consisted of 108 patients negative for COVID-19 throughout the entire hospitalization period, confirmed by daily PCR tests. This group included 36 patients receiving simple radiotherapy and 72 patients receiving chemoradiotherapy. The < 10-d COVID-19 group included 137 patients who received treatment within 10 days after their first positive COVID-19 test and who received treatment before COVID-19 infection and did not quit the treatment after the infection. In this group, 54 patients received simple radiotherapy, and 83 patients received chemoradiotherapy. The ≥ 10-d COVID-19 group consisted of 102 patients whose radiotherapy or chemoradiotherapy was initiated between 10 to 40 days after the first positive COVID-19 test. This group included 43 patients receiving simple radiotherapy and 59 patients receiving chemoradiotherapy. Patients who received anti-cancer therapy after 40 days were excluded. The duration of treatment delay was assessed from the time of the first positive COVID-19 nucleic acid or antigen test to the start of treatment. We included all COVID-19 cases reported in Shandong Cancer Hospital during the study period. The COVID-19 variants in this study were Omicron strains, which were detected by the Shandong Provincial Center for Disease Control and Prevention. COVID-19 infection was diagnosed based on the quick advice guide for the diagnosis and treatment of COVID-19 provided by the Chinese National Health Commission [17]. The specific protocols used for treating cancer patients based on their individual conditions and chemotherapy agents are summarized in Table 1. Informed consent was obtained from all patients, and the study was approved by the Ethics Committee of Shandong Cancer Hospital.
Table 1
The clinical characteristics of all cancer patients
Clinical characteristics | Non-COVID-19 group (n = 108) | < 10-d COVID-19 group (n = 137) | ≥ 10-d COVID-19 group (n = 102) | p value* |
Age (year) | 58.42 ± 12.81 | 57.86 ± 10.82 | 58.63 ± 11.09 | 0.8667 |
Sex, female (%) | 33 (30.56) | 65 (47.45) # | 35 (34.31) | 0.0160 |
Cancer type, n (%) | | | | 0.0578 |
Lung cancer | 46 (42.59) | 68 (49.64) | 55 (53.92) | |
Breast cancer | 9 (8.33) | 25 (18.25) # | 9 (8.82) | |
Esophageal cancer | 18 (16.67) | 10 (7.30) | 11 (10.78) | |
Head and neck cancer | 17 (15.74) | 12 (8.76) | 13 (12.75) | |
Brain cancer | 8 (7.41) | 5 (3.65) | 6 (5.88) | |
Other | 10 (9.26) | 17 (12.41) | 8 (7.84) | |
Radiotherapy position, n (%) | | | | 0.0175 |
Lung | 26 (24.07) | 30 (21.90) | 29 (28.43) | |
Breast and chest | 12 (11.11) | 30 (21.90) # | 12 (11.76) | |
Esophagus | 15 (13.89) | 7 (5.11) | 10 (9.80) | |
Head and neck | 19 (17.59) | 11 (8.03) | 12 (11.76) | |
Brain | 18 (16.67) | 29 (21.17) | 16 (15.69) | |
Bone | 13 (12.04) | 11 (8.03) | 13 (12.75) | |
Other | 5 (4.63) | 19 (13.87) | 10 (9.80) | |
Drug, n (%) | N = 72 | N = 83 | N = 59 | 0.0131 |
Taxol (plant alkaloids) /platinum/cytotoxicity | 47 (65.28) | 36 (43.37) # | 36 (61.02) | |
Targeting drugs | 16 (22.22) | 18 (21.69) | 15 (25.42) | |
Immunotherapy | 1 (1.39) | 10 (12.05) | 1 (1.69) | |
Endocrine therapy | 3 (4.17) | 11 (13.25) | 3 (5.08) | |
Other | 5 (6.94) | 8 (9.64) | 4 (6.78) | |
Duration of the delaying therapy after COVID-19 (d) | - | 3.02 ± 3.23 (0 ~ 9) | 16.36 ± 6.57 (10 ~ 39) | < 0.001 |
*p value was calculated by Mann-Whitney U test between two groups. Comparison among three groups was analyzed by one-way ANOVA test for normally distributed data, or Kruskal-Wallis test for abnormally distributed data. Chi square test was used for analyzing the rates. The numerical value was represented by Mean ± SD. #p < 0.05 vs. Non-COVID-19 group. |
Data collection
Three biochemical analyzers were utilized for measuring various biomarkers. The Beckman AU5800 automatic biochemical analyzer (Beckman Coulter, CA, USA) was used to measure inflammatory cytokines, such as serum amyloid protein A (SAA), high-sensitivity C-reactive protein (hsCRP), prealbumin (PA), cardiovascular injury-related biomarkers, including aspartate aminotransferase (AST), serum lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), creatine kinase (CK), and creatine kinase MB (CK-MB), and liver function biomarkers, including alanine aminotransferase (ALT), glutamyltransferase (GGT), adenosine deaminase (ADA), cholinesterase (CHE), and renal function biomarker creatinine (CREA). The Cobas e801 analyzer (Roche Diagnostics, GmbH, Mannheim, Germany) was used to measure the serum levels of ferritin, interleukin-6 (IL-6), procalcitonin (PCT), cardiac troponin-T (cTnT), and pro B-type natriuretic peptide (proBNP). Complete blood count (CBC) was assessed using a Sysmex XN9000 (Sysmex Corporation, Kobe, Japan) to measure white blood cell count (WBC), neutrophils (NEU), lymphocytes (LYM), lymphocyte percentage (LYM%), hemoglobin (HGB), platelets (PLT), and neutrophil to lymphocyte ratio (NLR).
Lymphocyte subtypes were determined using flow cytometry with a NAVIOS flow cytometer (Beckman Coulter, USA). The analyzed lymphocyte subtypes included NK cell (CD3-CD16 + CD56+), B cell (CD3-CD19+), total T cell (CD3+), Th cell (CD3 + CD4+), Tc/Ts cell (CD3 + CD8+), and the ratio of CD4+/CD8+, CD3 + CD4+/CD3+, CD3 + CD4 + CD25 + FOXP3+/CD3+, and CD3 + CD4 + CD25 + FOXP3+/CD3 + CD4+. Anti-CD3, anti-CD16, anti-CD56, anti-CD19, anti-CD4, anti-CD8, and anti-CD25 antibodies were used for flow cytometry (Tongsheng Shidai Biotech Co., Ltd, Beijing, China). The anti-FOXP3 antibody was obtained from MultiSciences Biotech Co., Ltd (Hangzhou, Zhejiang, China). All laboratory data were collected following the standard operating procedures in the clinical laboratory of Shandong Cancer Hospital.
Demographic and clinical data, including age, sex, cancer types, position of radiotherapy, duration of therapy delay, as well as laboratory results, were collected from the electronic medical record and laboratory information system (Ruimei LIS version 6.0, Shanghai, China).
Statistical analysis
Statistical analysis was performed using GraphPad Prism version 9.0 (GraphPad Software, CA, USA). The normality of all data was measured. Data are presented as mean ± SD. The Mann-Whitney U test was used to compare two groups with non-normal distribution. The Kruskal-Wallis test was utilized to compare three groups with non-normal distribution, while the one-way analysis of variance (ANOVA) test was employed for normally distributed data. The Chi-square test was utilized to compare rates. A p-value less than 0.05 was considered statistically significant.