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.

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.

SMARCB1 Gene Mutation Predisposes to Earlier Development of Glioblastoma: A Case Report of Familial GBM.

Glioblastoma (GBM) is the most aggressive adult brain tumor. While GBM typically occurs sporadically, familial GBM can be associated with certain hereditary disorders and isolated familial GBMs in the absence of syndrome are rare. Relevant hereditary factors have remained elusive in these cases. Understanding specific genetic abnormality may potentially lead to better treatment strategies in these patients. Here, we analyzed GBM tissue from our patient and 2 afflicted family members, with next generation sequencing to better understand the genetic alterations associated with this disease development. DNA was extracted and sequenced and the data were then analyzed. Results revealed 2 common mutations in afflicted family members; PDGFRA and HRAS. In addition, both siblings showed a mutation of the SMARCB1 gene. The sister of our patient exhibited a homozygous mutation, while our patient had heterozygous mutation of this gene in the tumor tissue. This result suggests that mutation of SMARCB1, either alone or in the presence of PDGFRA and HRAS mutations, is associated with earlier onset GBM.

A Focus of Differentiated Myeloid Sarcoma in a Ligation Specimen of the Fallopian Tube: No Evidence of Hematologic Abnormality in 18 Years of Follow-up Despite Absence of Treatment.

A 0.2-cm intramural focus composed predominantly of myelocytes and metamyelocytes, many CD3+, CD43+ T-lymphocytes, scanty CD20+ B-lymphocytes, rare mast cells, but no eosinophils or myeloblasts was incidentally found in a ligation specimen of the left fallopian tube. The myeloid cells were positive for chloroacetate esterase, myeloperoxidase, myeloid marker BM2, and CD43, and they were negative for CD30, CD34, CD117, ERG, and TDT. The findings in the left fallopian tube were consistent with the diagnosis of differentiated myeloid sarcoma. The right fallopian tube was normal. No hematologic abnormalities were found elsewhere in the body. Curiously, the patient remains free of any hematologic abnormality for 18 years despite absence of treatment.