Effect of Corticosteroid on Immunogenicity of SARS-CoV-2 Vaccines in Patients With Solid Cancer.

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.

Difference in Immunogenic Responses to COVID-19 Vaccines in Patients With Cancer Receiving Chemotherapy Versus Nonchemotherapy Treatment.

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.

Immunogenicity evaluation of ChAdox1 nCov-19 (AZD1222) vaccine in solid cancer patients in Chulabhorn Hospital.

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.

Age- and sex-specific genomic profiles in non-small cell lung cancer.

CONTEXT: Gene expression profiling may be useful in examining differences underlying age- and sex-specific outcomes in non-small cell lung cancer (NSCLC). OBJECTIVE: To describe clinically relevant differences in the underlying biology of NSCLC based on patient age and sex. DESIGN, SETTING, AND PATIENTS: Retrospective analysis of 787 patients with predominantly early stage NSCLC performed at Duke University, Durham, North Carolina, from July 2008 to June 2009. Lung tumor samples with corresponding microarray and clinical data were used. All patients were divided into subgroups based on age (< 70 vs > or = 70 years old) or sex. Gene expression signatures representing oncogenic pathway activation and tumor biology/microenvironment status were applied to these samples to obtain patterns of activation/deregulation. MAIN OUTCOME MEASURES: Patterns of oncogenic and molecular signaling pathway activation that are reproducible and correlate with 5-year recurrence-free patient survival. RESULTS: Low- and high-risk patient clusters/cohorts were identified with the longest and shortest 5-year recurrence-free survival, respectively, within the age and sex NSCLC subgroups. These cohorts of NSCLC demonstrate similar patterns of pathway activation. In patients younger than 70 years, high-risk patients, with the shortest recurrence-free survival, demonstrated increased activation of the Src (25% vs 6%; P<.001) and tumor necrosis factor (76% vs 42%; P<.001) pathways compared with low-risk patients. High-risk patients aged 70 years or older demonstrated increased activation of the wound healing (40% vs 24%; P = .02) and invasiveness (64% vs 20%; P<.001) pathways compared with low-risk patients. In women, high-risk patients demonstrated increased activation of the invasiveness (99% vs 2%; P<.001) and STAT3 (72% vs 35%; P<.001) pathways while high-risk men demonstrated increased activation of the STAT3 (87% vs 18%; P<.001), tumor necrosis factor (90% vs 46%; P<.001), EGFR (13% vs 2%; P = .003), and wound healing (50% vs 22%; P<.001) pathways. Multivariate analyses confirmed the independent clinical relevance of the pathway-based subphenotypes in women (hazard ratio [HR], 2.02; 95% confidence interval [CI], 1.34-3.03; P<.001) and patients younger than 70 years (HR, 1.83; 95% CI, 1.24-2.71; P = .003). All observations were reproducible in split sample analyses. CONCLUSIONS: Among a cohort of patients with NSCLC, subgroups defined by oncogenic pathway activation profiles were associated with recurrence-free survival. These findings require validation in independent patient data sets.

Genetic Aberration Analysis in Thai Colorectal Adenoma and Early-Stage Adenocarcinoma Patients by Whole-Exome Sequencing.

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.

Phase II Studies with Refametinib or Refametinib plus Sorafenib in Patients with RAS-Mutated Hepatocellular Carcinoma.

Purpose: Refametinib, an oral MEK inhibitor, has demonstrated antitumor activity in combination with sorafenib in patients with RAS-mutated hepatocellular carcinoma (HCC). Two phase II studies evaluated the efficacy of refametinib monotherapy and refametinib plus sorafenib in patients with RAS-mutant unresectable or metastatic HCC.Patients and Methods: Eligible patients with RAS mutations of cell-free circulating tumor DNA (ctDNA) determined by beads, emulsion, amplification, and magnetics technology received twice-daily refametinib 50 mg ± sorafenib 400 mg. Potential biomarkers were assessed in ctDNA via next-generation sequencing (NGS).Results: Of 1,318 patients screened, 59 (4.4%) had a RAS mutation, of whom 16 received refametinib and 16 received refametinib plus sorafenib. With refametinib monotherapy, the objective response rate (ORR) was 0%, the disease control rate (DCR) was 56.3%, overall survival (OS) was 5.8 months, and progression-free survival (PFS) was 1.9 months. With refametinib plus sorafenib, the ORR was 6.3%, the DCR was 43.8%, OS was 12.7 months, and PFS was 1.5 months. In both studies, time to progression was 2.8 months. Treatment-emergent toxicities included fatigue, hypertension, and acneiform rash. Twenty-seven patients had ctDNA samples available for NGS. The most frequently detected mutations were in TERT (63.0%), TP53 (48.1%), and ß-catenin (CTNNB1; 37.0%).Conclusions: Prospective testing for RAS family mutations using ctDNA was a feasible, noninvasive approach for large-scale mutational testing in patients with HCC. A median OS of 12.7 months with refametinib plus sorafenib in this small population of RAS-mutant patients may indicate a synergistic effect between sorafenib and refametinib-this preliminary finding should be further explored. Clin Cancer Res; 24(19); 4650-61. ©2018 AACR.

Primary peritoneal adenosarcoma with stromal overgrowth and fetal type cartilage: a case report and literature review.

Primary peritoneal adenosarcoma with sarcomatous overgrowth and fetal-type cartilage presented in a 48-year-old female patient is described. The tumor seems likely to have derived from the pelvic peritoneum, wheareas the uterus, ovaries and tubes were uninvolved. It was composed of benign-appearing glands and a sarcomatous component showing cartilaginous differentiation. The extrauterine adenosarcomas were reported in other sites, e.g. cervix, ovary, fallopian tube, bladder, and peritoneum. This case was the ninth case of the primary peritoneal adenosarcoma in the English literature and the first report in Thailand.

Emerging technologies for improved stratification of cancer patients: a review of opportunities, challenges, and tools.

Cancer is a heterogeneous collection of diseases with wild variation in etiology, pathogenesis, response to therapy, and prognosis. Sources of variation are frequently obscure. Current practice attempts to classify tumors by tissue of origin and extent of disease through staging such that more risky tumors can be managed with more aggressive treatments. Modest inroads have been made with biomarkers to further characterize groups of tumors with important characteristics such as response to selected drugs. However, biomarker-driven decisions are relatively few when examining the maze of clinical decisions in the care of cancer patients. Against this backdrop, waves of researchers have unleashed a vast array of new technologies, with the goal of better characterization of the inherent diversity of tumors. This review outlines the use of cancer biomarkers and emerging technologies to stratify patients with a focus on the challenges and opportunities of next-generation nucleic acid sequencing approaches in oncology.