Worawit Chaiwiriyawong’s research while affiliated with Chulabhorn Royal Academy and other places

PURPOSE Corticosteroids are known to diminish immune response ability, which is generally used in routine premedication for chemotherapy. The intersecting of timeframe between the corticosteroid's duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines to promote effective immunity in this population is needed. METHODS This was a prospective longitudinal observational cohort study that enrolled patients with solid cancer classified into dexamethasone- and nondexamethasone-receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in patients with cancer after two doses of COVID-19 vaccine in the dexamethasone and nondexamethasone group. Secondary outcomes included the postimmunization anti–spike (S) immunoglobin G (IgG) seroconversion rate, the association of corticosteroid dosage, time duration, and immunogenicity level. RESULTS Among the 161 enrolled patients with solid cancer, 71 and 90 were in the dexamethasone and nondexamethasone groups, respectively. The median anti–S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than that in the nondexamethasone group with a statistically significant difference (47.22 v 141.09 U/mL, P = .035). The anti–S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the nondexamethasone group (93.83% v 80.95%, P = .023). The lowest median anti–SARS-CoV-2 IgG titer level at 7.89 AU/mL was observed in patients with the highest dose of steroid group (≥37 mg of dexamethasone cumulative dose throughout the course of chemotherapy [per course]) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/mL. CONCLUSION Patients with solid cancer vaccinated against COVID-19 disease while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone. The direct association between the immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone, was observed.

127 Background: Corticosteroids are known to diminish immune response ability, which is generally used in routine pre-medication for chemotherapy. The intersecting of timeframe between the corticosteroid’s duration of action and peak COVID-19 vaccine efficacy could impair vaccine immunogenicity. Thus, inquiring about corticosteroids affecting the efficacy of vaccines, a dose of corticosteroids, and optimal timing of vaccination to promote effective immunity in this population is needed. Methods: This was a prospective longitudinal observational cohort study that enrolled solid cancer patients classified into dexamethasone and non-dexamethasone receiving groups. All participants were immunized with two doses of ChAdOx1 nCoV-19 or CoronaVac vaccines. This study's purpose was to compare corticosteroid's effect on immunogenicity responses to the SARS-CoV-2 S protein in solid cancer patients following two doses of COVID-19 vaccine in the dexamethasone and non-dexamethasone group. Secondary outcomes included the post-immunization anti-S IgG seroconversion rate, the association of corticosteroid dosage, time duration and immunogenicity level. Results: Among the 161 enrolled solid cancer patients, 71 and 90 were in the dexamethasone and non- dexamethasone groups, respectively. The median anti-S IgG titer after COVID-19 vaccination in the dexamethasone group was lower than non- dexamethasone group with a statistically significant difference (47.22 vs 141.09 U/ml, p = 0.035). The anti-S IgG seroconversion rate was also significantly lower in the dexamethasone group than in the non- dexamethasone group (93.83% vs 80.95% p = 0.023). The lowest median anti-SARS-CoV-2 IgG titer level at 7.89 AU/ml showed in patients with the highest dose of steroid group (37 mg or more of dexamethasone) and patients who were injected with COVID-19 vaccines on the same day of receiving dexamethasone, 25.41 AU/ml. Conclusions: Solid cancer patients vaccinated against COVID-19 while receiving dexamethasone had lower immunogenicity responses than those who got vaccines without dexamethasone, regardless of active cancer treatment types.The direct association between immunogenicity level and steroid dosage, as well as length of duration from vaccination to dexamethasone was observed. Clinical trial information: TCTR20221001004 .

Purpose: The COVID-19 pandemic has affected public health worldwide. The efficacy and safety of COVID-19 vaccines have been evaluated in the general population; however, data on patients with malignancies are limited. Methods: This prospective longitudinal observational cohort study was conducted between June and July 2021. Enrolled adult patients with cancer were divided into chemotherapy and nonchemotherapy groups. All participants were immunized with two doses of the ChAdOx1 nCoV-19 or CoronaVac COVID-19 vaccines. The primary outcome was a comparison of the immunogenicity (as assessed by spike protein [anti-S] immunoglobulin G [IgG] antibody titers) of two doses of COVID-19 vaccine in the chemotherapy and nonchemotherapy groups. The secondary outcomes included the anti-S IgG seroconversion rate and vaccine safety in both groups. Results: Among the 173 enrolled patients with solid cancer, after COVID-19 vaccination, the chemotherapy group had a significantly lower median anti-S IgG titer than the nonchemotherapy group (26 v 237 U/mL, P < .001). A statistically significant difference in anti-S IgG titer was found between groups vaccinated with CoronaVac (7 v 90 U/mL, P < .001), but no difference was found in those vaccinated with ChAdOx1 nCoV-19 (818 v 1061 U/mL, P = .075). The anti-S IgG seroconversion rate was significantly lower in the chemotherapy group than that in the nonchemotherapy group (78.9% v 96.5%, P = .001). No new or serious vaccine-related adverse events were reported. Conclusion: Patients with solid cancer receiving a COVID-19 vaccine while undergoing chemotherapy had lower immunogenicity responses to vaccination than those who were vaccinated while undergoing nonchemotherapy treatment. No statistically significant difference was observed in the COVID-19 vaccine safety profiles between groups.

Introduction Cancer patients are more vulnerable to coronavirus disease 2019 (COVID-19) owing to their compromised immune status. However, data regarding COVID-19 vaccine safety and immune response in cancer patients are scarce. Method This prospective, age- and sex-matched, single-center cohort study included 61 cancer patients and 122 healthy control participants. Seropositivity was defined as anti-S IgG titer >0.8 units/ml. Primary end point was seroconversion rate of immunoglobulin (Ig)G antibodies against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike (S) protein (anti-S IgG) in cancer patients vs. healthy control participants following the second dose of COVID-19 vaccine ChAdOx1 nCoV-19 (AZD1222). Results After the second-dose vaccination, there was no difference in seropositivity rate between groups (57 [93.44%] patients with cancer vs. 121 [99.18%] control participants; geometric mean ratio [GMR]: 0.39; 95%CI: 0.01–10.46; p-value = 0.571). In contrast, after the first-dose vaccination, the seropositivity rate was significantly lower in the cancer patients than in the control participants (50/61 [81.97%] vs. 121/122 [99.18%]; GMR: 0.07; 95%CI: 0.01–0.71; p = 0.025). The median anti-S IgG titer after the first-and second dose vaccination were not significantly different between groups. Female sex was significantly associated with a higher anti-S IgG titer. 5FU- and taxane-based chemotherapy regimens were associated with a lower IgG titer. Side effects of vaccination were tolerable. Conclusions The anti-S IgG seropositivity rate after completing the second vaccine dose did not differ between the cancer patients and control participants. However, the anti-S IgG seropositivity rate after the first-dose vaccination was lower in cancer patients.

Colorectal adenomas are precursor lesions of colorectal adenocarcinoma. The transition from adenoma to carcinoma in patients with colorectal cancer (CRC) has been associated with an accumulation of genetic aberrations. However, criteria that can screen adenoma progression to adenocarcinoma are still lacking. This present study is the first attempt to identify genetic aberrations, such as the somatic mutations, copy number variations (CNVs), and high-frequency mutated genes, found in Thai patients. In this study, we identified the genomic abnormality of two sample groups. In the first group, five cases matched normal-colorectal adenoma-colorectal adenocarcinoma. In the second group, six cases matched normal-colorectal adenomas. For both groups, whole-exome sequencing was performed. We compared the genetic aberration of the two sample groups. In both normal tissues compared with colorectal adenoma and colorectal adenocarcinoma analyses, somatic mutations were observed in the tumor suppressor gene APC (Adenomatous polyposis coli) in eight out of ten patients. In the group of normal tissue comparison with colorectal adenoma tissue, somatic mutations were also detected in Catenin Beta 1 (CTNNB1), Family With Sequence Similarity 123B (FAM123B), F-Box And WD Repeat Domain Containing 7 (FBXW7), Sex-Determining Region Y-Box 9 (SOX9), Low-Density Lipoprotein Receptor-Related Protein 5 (LRP5), Frizzled Class Receptor 10 (FZD10), and AT-Rich Interaction Domain 1A (ARID1A) genes, which are involved in the Wingless-related integration site (Wnt) signaling pathway. In the normal tissue comparison with colorectal adenocarcinoma tissue, Kirsten retrovirus-associated DNA sequences (KRAS), Tumor Protein 53 (TP53), and Ataxia-Telangiectasia Mutated (ATM) genes are found in the receptor tyrosine kinase-RAS (RTK–RAS) signaling pathway and p53 signaling pathway, respectively. These results suggest that APC and TP53 may act as a potential screening marker for colorectal adenoma and early-stage CRC. This preliminary study may help identify patients with adenoma and early-stage CRC and may aid in establishing prevention and surveillance strategies to reduce the incidence of CRC.

Background: Early-stage colon cancer is increasingly detected by colonoscopic screening. The development of adjuvant chemotherapy in patients with stage-TT colon cancer remains a challenge. Tn Thailand, the clinicopathological risk factors [CPR] are currently used as criteria for the selection of adjuvant chemotherapy in each patient. Previous reports showed that mismatch repair gene [MMR] status could be a prognostic factor for the decision on adjuvant chemotherapy. Objective: To determine the characteristics of MMR status and CPR of Thai colon cancer cases, with treatment follow-up in stage-TT colon cancer by MMR and CPR. Materials and Methods: This was a preliminary report of patients with stage-TT colon cancer who received treatment at Chulabhorn Hospital. MMR status was determined by microsatellite instability [MST] testing and CPR was determined in each patient. Patients with deficient MMR and low CPR received post-surgery surveillance whereas those with proficient MMR and/or high CPR were treated with adjuvant chemotherapy (5-FU/LV). The follow-up of adverse events, serious adverse events, disease-free survival [DFS], and overall survival [OS] was at the third and fifth years. Results: During July 4, 2014 to December 31, 2016, there were 31 cases of stage-TT colon cancer. All of them were at the stage of T3NoMo (TTA). High CPR and low CPR were found in 20 cases (64.52%) and 11 cases (35.48%), respectively. There were 28 cases with MMR testing results. Proficient MMR (MST-low) was observed in 23 cases (82.14%). There were 3 cases with disease recurrence, all of which were in proficient MMR group and received adjuvant chemotherapy. Serious adverse events were found in 2 cases with infection during febrile neutropenia after chemotherapy but no treatment-related death was observed. DFS and OS could not yet be evaluated. Conclusion: Tncidence of proficient MMR (MST-low) in Thai patients with stage-TT colon cancer was comparable to that of other countries (80 to 90%). Treatment by adjuvant chemotherapy using MMR status and CPR was feasible with low serious adverse events.