Improved Pathologic response to chemoradiation in MGMT methylated locally advanced rectal cancer.

Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0-1 considered to have excellent response and grades of 2-3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.

Molecular detection of the COVID-19 genome in prostatic tissue of patients with previous infection.

COVID-19 infection has been linked to worsening or de novo lower urinary tract symptoms and transient serum prostate-specific antigen rise in patients with benign prostatic hyperplasia. This pilot study aimed to examine prostatic tissue for evidence for direct involvement with the COVID-19 (SARS-CoV-2) infection. Fourteen patients with previous documented COVID-19 infection who underwent prostate enucleation had their prostate specimens examined for COVID-19 RNA. The specimens were examined using a SARS-CoV-2 test, an in vitro diagnostic test based on reverse transcription polymerase chain reaction technology that analyses the presence of RNA for the SARS-CoV-2 strain. Among the 14 patients, COVID infection was severe in three, mild in seven, and asymptomatic in four patients. The COVID-19 genome was successfully identified in the prostate specimen of a single patient. Although this patient had mild COVID-19 infection, he had positive COVID tests for 40 days after the initial infection. Identification of the COVID-19 genome in prostate tissue is a further step toward better understanding its effect on the genitourinary tract. This study's findings provide some explanation for the proposed association with lower urinary tract symptoms and rise in serum prostate-specific antigen levels. Larger studies are needed to further investigate this association.

Vaccine effectiveness against COVID-19 among symptomatic persons aged ≥12 years with reported contact with COVID-19 cases, February-September 2021.

BACKGROUND: Individuals in contact with persons with COVID-19 are at high risk of developing COVID-19; protection offered by COVID-19 vaccines in the context of known exposure is poorly understood. METHODS: Symptomatic outpatients aged ≥12 years reporting acute onset of COVID-19-like illness and tested for SARS-CoV-2 between February 1 and September 30, 2021 were enrolled. Participants were stratified by self-report of having known contact with a COVID-19 case in the 14 days prior to illness onset. Vaccine effectiveness was evaluated using the test-negative study design and multivariable logistic regression. RESULTS: Among 2229 participants, 283/451 (63%) of those reporting contact and 331/1778 (19%) without known contact tested SARS-CoV-2-positive. Adjusted vaccine effectiveness was 71% (95% confidence interval [CI], 49%-83%) among fully vaccinated participants reporting a known contact versus 80% (95% CI, 72%-86%) among those with no known contact (p-value for interaction = 0.2). CONCLUSIONS: This study contributes to growing evidence of the benefits of vaccinations in preventing COVID-19 and support vaccination recommendations and the importance of efforts to increase vaccination coverage.

Surveillance genome sequencing reveals multiple SARS-CoV-2 variants circulating in central Texas, USA, with a predominance of delta variant and review of vaccine breakthrough cases.

As surges in the COVID-19 pandemic have continued worldwide, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has mutated, spawning several new variants, and impacting, to various degrees, transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. Baylor Scott & White Health has implemented, along with laboratory diagnosis, SARS-CoV-2 sequencing to identify variants in its geographical service area. We analyzed virus sequencing results of specimens collected across Central Texas and found dramatic changes in variant distribution in the first half of 2021. The alpha variant (B 1.1.7) became predominant at week 13 and continued dominance until week 25. A growth rate of 1.20 (R2 = 0.92) for the first 15 weeks was noted and this growth gradually declined to -0.55 (R2 = 0.99) for the final 13 weeks. Currently, B.1.1.7 is being displaced with B.1.617.2 at a 0.58 growth rate (R2 = 0.97). We also investigated vaccine breakthrough cases (VBCs) within our healthcare system and present clinical data on 28 symptomatic patients.

Improved local control in p16 negative oropharyngeal cancers with hypermethylated MGMT.

INTRODUCTION: Patients with oropharyngeal cancers that are p16 negative (p16-) have worse outcomes than those who are p16 positive (p16+) and there is an unmet need for prognostic markers in this population. O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated with response to chemoradiotherapy (CRT) in glioblastoma. We sought to find if MGMT promoter methylation was associated with outcomes of locally advanced oropharyngeal and oral cavity squamous cell carcinoma (OOSCC) in patients treated with definitive concurrent CRT. METHODS: Patients were identified with primary OOSCC, known p16 status, retrievable pre-treatment biopsies, and at least 6 months of follow-up who received definitive concurrent CRT from 2004 to 2015. Biopsies were tested for MGMT hypermethylation (MGMT+) using a Qiagen pyrosequencing kit (Catalog number 970061). Outcomes were subsequently recorded and analyzed. RESULTS: Fifty-eight patients were included with a median follow up of 78 (range 6-196) months. Fourteen patients (24.1%) had oral cavity cancer and 44 (75.9%) had oropharyngeal cancer. A significant difference was found for local recurrence free survival (LRFS) by combined MGMT and p16 status (p = 0.0004). Frequency of LR in MGMT+/p16+, MGMT+/p16-, MGMT-/p16+, and MGMT-p16- patients was 14.3%, 14.3%, 13.0%, and 69.2%, respectively (p = 0.0019). A significant difference was not found for distant recurrence free survival (p = 0.6165) or overall survival (p = 0.1615). LRFS remained significant on analysis restricted to oropharyngeal cancer patients (p-value = 0.0038). CONCLUSION: Patients who are p16- and MGMT+ with oropharyngeal and oral cavity squamous cell carcinoma have significantly better LC with definitive CRT than those who are p16- and MGMT-. Prospective studies are needed to verify these findings.