Safety Following COVID-19 Booster Vaccine with BNT162b2 Compared to mRNA-1273 in Solid Cancer Patients Previously Vaccinated with ChAdOx1 or CoronaVac.

Safety data following the COVID-19 booster mRNA vaccine in solid cancer patients are scarce. We prospectively evaluated adverse events after a booster dose of the BNT162b2 vaccine as compared to the mRNA-1273 vaccine in solid malignancy patients who had previously received two doses of ChAdOx1 or heterogenous CoronaVac/ChAdOx1. Data regarding solicited and unsolicited adverse events were collected using questionnaires. The primary endpoint was the difference in incidence and severity of adverse events between BNT162b2 and mRNA-1273 vaccines. A total of 370 subjects were enrolled, including 172 (47%) and 198 (54%) patients receiving booster doses of BNT162b2 and mRNA-1273 vaccines, respectively. The overall incidence of adverse events in the two groups was comparable (BNT162b2 vs. mRNA-1273; 63% vs. 66%, p = 0.6). There was no significant difference in severity, and the majority of adverse events reported were classed as mild to moderate. Tenderness at the injection site was the only reaction that had a statistically higher reported incidence after the mRNA-1273 vaccine than after the BNT162b2 vaccine (56% vs. 41%, p = 0.003). In conclusion, a booster dose of the mRNA vaccine, either BNT162b2 or mRNA-1273, in solid cancer patients previously vaccinated with ChAdOx1 and CoronaVac appears safe, and no new safety concerns were observed.

Safety and Immunogenicity of Homologous and Heterologous Adenoviral-Vectored and mRNA COVID-19 Vaccine Regimens in Radiotherapy Patients.

Diminished immune response after vaccination occurs in cancer patients. This observational study evaluated the immune response and safety profile after COVID-19 vaccination in radiotherapy patients. The study comprised 53 cancer patients undergoing radiotherapy and voluntarily received the COVID-19 vaccine. The two regimens were homologous ChAdOx1-S recombinant (AstraZeneca, AZ), "AZ-AZ" and heterologous "AZ-mRNA". The seroconversion rate and anti-RBD immunoglobulin geometric mean titers (GMT) were assessed and compared with healthy controls. Adverse effects were assessed using a questionnaire. The seroconversion rate was 52.4% 1 month after the first dose with GMT 4.3 U/mL (95%CI 1.4-13). Following the second dose, the AZ-AZ group achieved 95% seroconversion rate with GMT = 188.4 U/mL (95%CI 67.1-529), which was significantly lower than the healthy cohort, GMT = 945 U/mL (95%CI 708-1261). Cancer patients in AZ-mRNA group achieved a 100% seroconversion rate with a high GMT = 1400.8 U/mL (95%CI 429.5-4566), which was significantly lower than the healthy cohort, GMT = 5169.9 U/mL (95%CI 3582.2-7461.5). Most adverse effects were mild. Our findings suggest that radiotherapy patients had fair immunogenicity after the first dose, but achieved a high seroconversion rate after the second dose with manageable adverse effects. However, their immunologic response was lower than in healthy individuals, indicating that other preventive strategies are needed.

A prospective randomized study comparing the efficacy between povidone-iodine gargling and benzydamine hydrochloride for mucositis prevention in head and neck cancer patients receiving concurrent chemoradiotherapy.

Background: Concurrent chemoradiation (CCRT) has been the standard treatment for organ preservation or locally advanced head and neck cancer (LAHNC). Radiation-induced oral mucositis (RIOM) is an important treatment-limiting toxicity. Benzydamine hydrochloride was recommended to prevent oral mucositis. Povidone-iodine had also been adopted to use as an oral rinse to prevent mucositis. Objective: This study compared the efficacy between benzydamine hydrochloride and 0.1% povidone-iodine to prevent RIOM in HNC patients who received concurrent chemoradiotherapy. Methods: We conducted a randomized control study in HNC patients receiving CCRT with curative intent. The stratification factors were primary site of disease, treatment modality, chemotherapy regimen, and schedule. The primary outcome was RIOM assessed by Oral Mucositis Assessment Scale (OMAS). Secondary outcomes included RIOM assessed by NCI-CTCAE, use of analgesic, antibiotics and anti-fungal drugs, hospitalization, and participant satisfaction. Results: There were 83 participants recruited for this study with 71 completing the trial. Demographic characteristics were well-balanced between both arms. The univariate regression analysis revealed that povidone-iodine correlated with less RIOM compared to benzydamine hydrochloride (coefficient -2.25, 95% CI -4.37 to -0.012, p-value 0.03). The incidence of grade III-IV CTCAE RIOM during the study period was 51.4% with benzydamine hydrochloride compared to 26.5% with 0.1% povidone iodine (p-value 0.032). The peak incidence of grade III-IV CTCAE RIOM occurred in the 7th week of treatment (40.5% vs. 11.8%, p-value 0.01). This indicated the efficacy of povidone-iodine to prevent severe RIOM which usually most severity in the last week of CCRT treatment. The multivariate analysis revealed that the CCRT setting (definitive vs. adjuvant) and gargling agents (povidone-iodine vs. benzydamine hydrochloride were the factors associated with RIOM. Conclusion: This study demonstrated higher efficacy of 0.1% povidone-iodine gargle than benzydamine hydrochloride in mucositis prevention.

Differential expression of immune-regulatory proteins C5AR1, CLEC4A and NLRP3 on peripheral blood mononuclear cells in early-stage non-small cell lung cancer patients.

Changes in gene expression profiling of peripheral blood mononuclear cells (PBMC) appear to represent the host's response to the cancer cells via paracrine signaling. We speculated that protein expression on circulating T-lymphocytes represent T-lymphocyte trafficking before infiltration into the tumor microenvironment. The possibility of using protein expression on circulating T-lymphocytes as a biomarker to discriminate early-stage non-small cell lung cancer (NSCLC) was explored. Four independent PBMC gene expression microarray datasets (GSE12771, GSE13255, GSE20189 and GSE3934) were analyzed. We selected C5AR1, CLEC4A and NLRP3 based on their significant protein expression in tumor-infiltrating lymphocytes, but not in normal lymphoid tissue. A validation study using automated flow cytometry was conducted in 141 study participants including 76 treatment-naive early-stage non-small cell lung cancer patients (NSCLC), 12 individuals with non-malignant pulmonary diseases, and 53 healthy individuals. Median ratios of C5AR1, CLEC4A and NLRP3 specific antibody staining to CD3 positive cells in early-stage NSCLC patients compared to healthy controls were 0.014 [0-0.37] vs. 0.01 [0-0.07, p = 0.13], 0.03 [0-0.87] vs. 0.02 [0-0.13, p = 0.10] and 0.19 [0-0.60] vs. 0.09 [0.02-0.31, p < 0.0001], respectively. Median fluorescence intensity (MFI) of CD3+C5AR1+, CD3+CLEC4A+ and CD3+NLRP3+ expression in early-stage NSCLC patients compared to healthy volunteers was 185 [64.2-4801] vs. 107.5 [27-229, p < 0.0001], 91.2 [42.4-2355] vs. 71.25 [46.2-103, p = 0.0005], and 1585 [478-5224] vs. 758.5 [318-1976, p < 0.0001], respectively. NLRP3:CD3 ratio, CD3+C5AR1+, CD3+CLEC4A+ and CD3+NLRP3+ MFI were significantly higher in early-stage NSCLC than healthy volunteers with an area under the ROC curve of 0.69-0.76. The CD3+NLRP3+ MFI provided the most distinguishable expression at 71.5% sensitivity and 70% specificity. Furthermore, CD3+NLRP3+ MFI potentially discriminated between early-stage NSCLC from malignant-mimic inflammation and infection pulmonary disease. Further validation in various pulmonary inflammatory disease might be warranted. Our proof-of-principle findings strengthen the hypothesis that malignancies generate distinctive protein expression fingerprints on circulating T-lymphocytes.

Prognostic factors in completely resected lymph-node-negative pulmonary adenocarcinoma.

Background: Lymph node involvement is one of the important prognostic factors for early-stage lung cancer. However, in lymph node-negative (N0) lung cancer the recurrent rate may be as high as 30%. We aimed to study potential prognostic factors including clinicopathological factors and epidermal growth factor receptor (EGFR) mutation status in this lung cancer population. Methods: We retrospectively reviewed the medical records and pathological examinations of patients with completely resected N0 pulmonary adenocarcinoma treated in our institute between 2009 and 2016. We used Cobas® test to determine EGFR mutation status. Recurrence-free survival (RFS) was analyzed by univariable and multivariable Cox regression analyses. Results: We recruited 220 patients with median duration of follow up 5 years. Majority of these patients were in stage I (80%) and did not receive adjuvant therapy (86%). There were 53% with EGFR mutations which comprised of exon 19 deletion 51% and L858R 43%. Recurrence occurred in 64 out of 220 patients (29%). The median time to recurrence was 2.1 years. Statistically significant prognostic factors in both univariate and multivariate analyses included tumor size ≥4 centimeter (cm) (HR: 1.94; 95% CI: 1.03-3.67), visceral pleural invasion (HR: 2.53; 95% CI: 1.34-4.79), tumor necrosis (HR: 2.45; 95% CI: 1.13-5.31) and bronchial resection margin <2 cm (HR: 1.96; 95% CI: 1.10-3.51). However, presence of sensitizing EGFR mutation was not found to be a significant prognostic factor (HR: 1.20; 95% CI: 0.66-2.18; P=0.56). Conclusions: In N0 surgically resected lung adenocarcinoma, there were significant pathological prognostic factors including tumor 4 cm or more, visceral pleural invasion, tumor necrosis and bronchial resection margin less than 2 cm. Mutation of EGFR is not a significant prognostic factor to determine the risk of recurrence in this population and their risks shall be determined by the other poor prognostic factors.

Vaccine-Related adverse events following AZD1222 (ChAdOx1-nCoV-19) Covid-19 vaccine in solid malignancy patients receiving cancer treatment, as compared to age-matched healthy controls.

The study aimed to evaluate vaccine-related adverse events (VRAEs) following ChAdOx1-nCoV-19 vaccine in solid cancer patients receiving treatment compared to healthy controls. 399 cancer patients and 90 healthy volunteers were enrolled. In the overall population, the incidence of VRAEs was significantly lower in cancer patients than in healthy volunteers (57% vs 80%, P < .001). Because the mean age of the cancer patients was higher than the healthy volunteers (59 vs 48 years, P < .001), we analyzed age-matched comparison and found that there was no significant difference of VRAEs between two groups (74% vs 79%, P .32). Most VRAEs were of mild severity in both groups. The most common local VRAE was pain at the injection site in both groups, and the most common systemic VRAE was fatigue in the cancer cohort, while myalgia was the most common VRAE among the healthy controls. In the cancer cohort, fever was the only VRAE that led to interruption of the cancer treatment (in two cases). Among the cancer treatment types, patients undergoing chemotherapy-containing regimens had a lower likelihood of experiencing VRAEs. In summary, the overall incidence of VRAEs following ChAdOx1-nCoV-19 vaccine in actively treated cancer patients was comparable to healthy controls after adjusting for age. The VRAEs that occurred rarely interfered with the cancer treatment. These findings substantiate that vaccination with AZD1222 is safe in cancer patients undergoing treatment.

Efficacy, Safety, and Patient-Reported Outcomes of Atezolizumab Plus Bevacizumab for Unresectable Hepatocellular Carcinoma in Thailand: A Multicenter Prospective Study.

PURPOSE: Atezolizumab plus bevacizumab treatment is a first-line therapy for unresectable hepatocellular carcinoma (HCC) worldwide. The efficacy, safety, and patient-reported outcomes (PROs) of HCC in Thailand have not yet been reported. This study aimed to evaluate the efficacy, safety, and PROs of atezolizumab plus bevacizumab. MATERIALS AND METHODS: From September 2020 to August 2021, 30 patients with unresectable HCC who met the inclusion criteria of atezolizumab plus bevacizumab as first-line treatment were enrolled. Analysis was assessed for progression-free survival, overall survival, adverse events (AEs), and quality of life (QoL). RESULTS: The median progression-free survival and overall survival periods were 6.7 and 10.2 months, respectively. The disease control rate was 63.3%. The frequent AEs were proteinuria, hypertension, and hepatitis. Serious AEs included gastrointestinal bleeding, but none of the patients died from serious AEs. The discontinuation rate was 23.3%, and the median number of treatment cycles was 10.5 cycles. In total, 23.3% of the patients continued treatment after 1 year of therapy. The global health status/QoL and physical function scores showed less deterioration at baseline than at 3 and 6 months (median scores = 76.7, 71.6, and 64.1 in QoL and 84.7, 79.6, and 79.0 in physical function, respectively). The HCC18 symptom score index data showed a slow progression of symptom scores from baseline to 3 and 6 months (12.7, 19.6, and 22.3, respectively). CONCLUSION: This study demonstrates that atezolizumab plus bevacizumab is effective and has a safety profile comparable with that of previous studies as first-line therapy for unresectable HCC in a real-world setting and in Thai populations. Data on PROs also demonstrate benefits in terms of patients' QoL and symptoms.

Immunogenicity after a Third COVID-19 mRNA Booster in Solid Cancer Patients Who Previously Received the Primary Heterologous CoronaVac/ChAdOx1 Vaccine.

No data regarding the efficacy of a third mRNA vaccine for solid cancer patients previously primed with the heterologous CoronoVac/ChAdOx1 vaccination implemented in Thailand during the shortage of vaccine supply are available. Forty-four cancer patients who previously received the heterologous CoronaVac-ChAdOx1 regimen were boosted with a third mRNA COVID vaccine, either BNT162b2 or mRNA-1273. Anti-RBD IgG was measured immediately before, two weeks after, and four weeks after the third dose. The antibody response was compared to 87 age- and gender-matched cancer patients who were primed with the homologous ChAdOx1/ChAdOx1 regimens. Post-third dose anti-RBD IgG levels significantly increased compared to pre-third dose levels. There was no statistical difference in post-third dose antibody titers or neutralization levels between these two primary series regimens. Treatment with chemotherapy was associated with a lower antibody response compared to endocrine therapy/biologics. Similar antibody levels were observed after a third booster with either BNT162b2 or mRNA-1273 following heterologous CoronaVac/ChAdOx1 vaccination. There was no statistical difference in the immune response following the third-dose vaccination between cancer patients and healthy individuals who received the same heterologous CoronaVac/ChAdOx1 vaccination. In conclusion, a similar degree of enhanced immunogenicity was observed after a third mRNA COVID-19 vaccination in solid cancer patients who previously received the heterologous CoronaVac/ChAdOx1 regimens.

Durability of Immune Response to ChAdOx1-nCoV-19 Vaccine in Solid Cancer Patients Undergoing Anticancer Treatment.

There are limited data available about the durability of the immune response after administration of the widely used adenovirus-vectored ChAdOx1-nCoV-19 vaccine in cancer patients. This prospective longitudinal observational study analyzed follow-up data of immunogenic responses 12 weeks after the second dose of the ChAdOx1-nCoV-19 vaccine in 290 oncological patients compared to healthy controls. The study aimed to assess the persistence of the humoral immune response three months after the second dose, and omicron neutralization was also evaluated. Three months after completion of the second vaccine dose, the geometric mean titer of SARS-CoV-2 binding total Ig statistically decreased by 42% compared to those at 4 weeks, and was lower than that of the healthy control. Six percent of patients became seronegative for anti-RBD total Ig. Only 5% (2 of 40 samples) tested positive for surrogate neutralization against SAR-CoV-2 Omicron BA.2. Across different therapy types, a waning in immunogenicity was observed within three months after the second dose of the ChAdOx1 nCoV-19 vaccine, rendering it insufficient at that point to protect against the SAR-CoV-2 Omicron BA.2 variant.

Immunogenicity of ChAdOx1-nCoV-19 vaccine in solid malignancy patients by treatment regimen versus healthy controls: A prospective, multicenter observational study.

Background: Limited data exists regarding the efficacy of ChAdOx1-nCoV-19 vaccine against Severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) in solid cancer patients. We aimed to assess the immunogenicity of the ChAdOx1-nCoV-19 vaccine and the impact of different anticancer therapies for solid malignancies on immune response. Methods: This prospective, longitudinal observational study of immunogenicity following ChAdOx1-nCoV-19 vaccination among 385 solid cancer patients on active cancer treatment was conducted in two oncology centers. Participants received the first dose between June 18 and July 27, 2021 and the second dose at 8-10 weeks later. Blood samples were evaluated for total immunoglobulins against the receptor-binding of SARS-CoV-2 spike protein (anti-RBD total-Ig) before, and 4-week after the first- and second-doses. The primary endpoint was the geometric mean titers (GMT) of antibody among solid cancer patients compared to healthy controls and the impact of different cancer treatment types. Findings: Among solid cancer patients, the antibody level increased more slowly to significantly lower levels than achieved in healthy controls. The GMT at 4-weeks post-vaccination in cancer vs. healthy were 224.5 U/ml (95%CI 176.4-285.6) vs. 877.1 U/ml (95%CI 763.5-1008), p<0.0001), respectively. For different types of cancer treatments, chemotherapy agents, especially anthracyclines (GMR 0.004; 95%CI 0.002-0.008), paclitaxel (GMR 0.268; 95%CI 0.123-0.581), oxaliplatin (GMR 0.340; 95%CI 0.165-0.484), and immunotherapy (GMR 0.203; 95%CI 0.109-0.381) showed significantly lower antibody response. Anti-HER2, endocrine therapy and 5-fluouracil or gemcitabine, however, had less impact on the immune response. Interpretation: Suboptimal and heterogeneous immunologic responses were observed in cancer patients being treated with different systemic treatments. Immunotherapy or chemotherapy significantly suppressed the antibody response. Funding: Quality Improvement Fund, King Chulalongkorn Memorial Hospital, The Thai Red Cross Society and Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Medical Oncology Research Fund.