Dosimetric and toxicity comparison between Syed-Neblett and Fletcher-Suit-Delclos Tandem and Ovoid applicators in high dose rate cervix cancer brachytherapy.

PURPOSE: To compare patient and tumor characteristics, dosimetry, and toxicities between interstitial Syed-Neblett and intracavitary Fletcher-Suit-Delclos Tandem and Ovoid (T&O) applicators in high dose rate (HDR) cervical cancer brachytherapy. METHODS: A retrospective analysis was performed for cervical cancer patients treated with 3D-based HDR brachytherapy from 2011 to 2023 at a single institution. Dosimetric parameters for high-risk clinical target volume and organs at risk were obtained. Toxicities were evaluated using the Common Terminology Criteria for Adverse Events version 5.0. RESULTS: A total of 115 and 58 patients underwent Syed and T&O brachytherapy, respectively. Patients treated with Syed brachytherapy were more likely to have larger tumors and FIGO stage III or IV disease. The median D2cc values to the bladder, small bowel, and sigmoid colon were significantly lower for Syed brachytherapy. Patients treated with Syed brachytherapy were significantly more likely to be free of acute gastrointestinal (44% vs. 21%, p = 0.003), genitourinary (58% vs. 36%, p = 0.01), and vaginal toxicities (60% vs. 33%, p = 0.001) within 6 months following treatment compared to patients treated with T&O applicators. In contrast, Syed brachytherapy patients were more likely to experience late gastrointestinal (68% vs. 49%, p = 0.082), genitourinary (51% vs. 35%, p = 0.196), and vaginal toxicities (70% vs. 57%, p = 0.264). CONCLUSIONS: Syed-Neblett and T&O applicators are suitable for HDR brachytherapy for cervical cancer in distinct patient populations. Acute toxicities are more prevalent with T&O applicators, while patients treated with Syed-Neblett applicators are more likely to develop late toxicities.

Demographic variations and time to initiation of adjunct treatment following surgical resection of anaplastic astrocytoma in the United States: a National Cancer Database analysis.

BACKGROUND AND AIMS: The aim of this study was to analyze the trends, demographic differences in the type and time to initiation (TTI) of adjunct treatment AT following surgery for anaplastic astrocytoma (AA). MATERIAL AND METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with AA from 2004 to 2016. Cox proportional hazards and modeling was used to determine factors influencing survival, including the impact of time to initiation (TTI) of adjuvant therapy. RESULTS: Overall, 5890 patients were identified from the database. The use of combined RT + CT temporally increased from 66.3% (2004-2007) to 79% (2014-2016), p < 0001. Patients more likely to receive no treatment following surgical resection included elderly (> 60 years old), hispanic patients, those with either no or government insurance, those living > 20 miles from the cancer facility, those treated at low volume centers (< 2 cases/year). AT was received following surgical resection within 0-4 weeks, 4.1-8 weeks, and > 8 weeks in 41%, 48%, and 3%, respectively. Compared to patients who received RT + CT, patients were likely to receive RT only as AT either at 4-8 weeks or > 8 weeks after the surgical procedure. Patients who received AT within 0-4 weeks had the 3-year OS of 46% compared to 56.7% for patients who received treatment at 4.1-8 weeks. CONCLUSION: We found significant variation in the type and timing of adjunct treatment following surgical resection of AA in the United States. A considerable number of patients (15%) received no AT following surgery.

Patterns of care and outcomes of radiotherapy or hormone therapy in patients with medically inoperable endometrial adenocarcinoma.

OBJECTIVE: The optimal treatment for medically inoperable endometrioid endometrial adenocarcinoma is unknown. The goal of this study was to evaluate the patterns of care and efficacy of radiotherapy (RT) or hormone therapy (HT) in the treatment of these patients. METHODS: We performed a query of the National Cancer Database (NCDB) of patients with medically inoperable endometrioid adenocarcinoma of the endometrium diagnosed between 2004 and 2016 and treated with either RT or HT. A multivariate Cox regression model and propensity weighted analyses were used to evaluate overall survival after controlling for confounding variables. A multinomial logistic regression model was used to assess predictors of RT or HT use. RESULTS: A total of 1036 patients were included in this cohort, and 73% (n = 759) were treated with RT alone. Patients who received definitive HT compared to RT were more likely to be older, diagnosed in the earlier years of this analysis, treated at lower-case volume centers, diagnosed with high-grade disease, or located outside of metropolitan areas. On multivariate analysis, treatment with HT alone versus RT alone was associated with significantly worse overall survival in the multivariate Cox model but not on propensity score weighted analysis. Interaction effect testing revealed that older patients and those treated at lower-volume centers had improved survival with RT compared to HT. CONCLUSIONS: We identified factors associated with the receipt of RT or HT in medically inoperable endometrial cancer patients. Treatment with RT correlated with improved survival compared to HT in older patients and those treated at lower-volume centers.

CK7 negative anaplastic thyroid carcinoma presenting as cutaneous metastases to the scalp.

Anaplastic thyroid carcinoma (ATC) is an extremely rare but aggressive form of thyroid cancer. Although local tissue invasion is characteristic of this disease, systemic metastases are a common clinical finding. Our case discusses an unusual presentation of cutaneous metastases to the scalp in a patient with a remote history of ATC. It also highlights the utility of immunohistochemical staining in determining the origin of a tumor when the source of primary malignancy is not readily identifiable.

Genetic variation in the 5'UTR of the KRT2.13 gene of sheep.

KRT2.13 is a type II keratin wool intermediate filament (IF) protein. Extensive variation was revealed in the 5' untranslated region (UTR) of the ovine KRT2.13 gene (KRT2.13) using polymerase chain reaction - single strand conformational polymorphism (PCR-SSCP) analysis. Nine unique PCR-SSCP patterns were obtained with individual sheep having either one (homozygous), or a combination of two (heterozygous) of these patterns. Seven of the amplicons that produced the apparently homozygous patterns were successfully sequenced (GenBank FJ217670 - FJ217676), revealing eight single nucleotide insertions, 10 single nucleotide substitutions, a nucleotide deletion and a 16 nucleotide insertion that occurred in only one of the sequences. The seven sequences showed between 85% and 95% homology to the previously identified KRT2.13 sequence (GenBank X72379). This study emphasizes the power of PCR-SSCP analysis in genotyping, as this extensive variation was found in only 100 sheep, of a variety of breeds. Since variation in the 5'UTR of genes may affect their expression, this genetic variation needs to be further studied to establish its role if any, in influencing gene expression and consequently wool traits.

An updated nomenclature for keratin-associated proteins (KAPs).

Most protein in hair and wool is of two broad types: keratin intermediate filament-forming proteins (commonly known as keratins) and keratin-associated proteins (KAPs). Keratin nomenclature was reviewed in 2006, but the KAP nomenclature has not been revised since 1993. Recently there has been an increase in the number of KAP genes (KRTAPs) identified in humans and other species, and increasingly reports of variation in these genes. We therefore propose that an updated naming system is needed to accommodate the complexity of the KAPs. It is proposed that the system is founded in the previous nomenclature, but with the abbreviation sp-KAPm-nL*x for KAP proteins and sp-KRTAPm-n(p/L)*x for KAP genes. In this system "sp" is a unique letter-based code for different species as described by the protein knowledge-based UniProt. "m" is a number identifying the gene or protein family, "n" is a constituent member of that family, "p" signifies a pseudogene if present, "L" if present signifies "like" and refers to a temporary "place-holder" until the family is confirmed and "x" signifies a genetic variant or allele. We support the use of non-italicised text for the proteins and italicised text for the genes. This nomenclature is not that different to the existing system, but it includes species information and also describes genetic variation if identified, and hence is more informative. For example, GenBank sequence JN091630 would historically have been named KRTAP7-1 for the gene and KAP7-1 for the protein, but with the proposed nomenclature would be SHEEP-KRTAP7-1*A and SHEEP-KAP7-1*A for the gene and protein respectively. This nomenclature will facilitate more efficient storage and retrieval of data and define a common language for the KAP proteins and genes from all mammalian species.

Genetic diversity of selected genes that are potentially economically important in feral sheep of New Zealand.

BACKGROUND: Feral sheep are considered to be a source of genetic variation that has been lost from their domestic counterparts through selection. METHODS: This study investigates variation in the genes KRTAP1-1, KRT33, ADRB3 and DQA2 in Merino-like feral sheep populations from New Zealand and its offshore islands. These genes have previously been shown to influence wool, lamb survival and animal health. RESULTS: All the genes were polymorphic, but no new allele was identified in the feral populations. In some of these populations, allele frequencies differed from those observed in commercial Merino sheep and other breeds found in New Zealand. Heterozygosity levels were comparable to those observed in other studies on feral sheep. Our results suggest that some of the feral populations may have been either inbred or outbred over the duration of their apparent isolation. CONCLUSION: The variation described here allows us to draw some conclusions about the likely genetic origin of the populations and selective pressures that may have acted upon them, but they do not appear to be a source of new genetic material, at least for these four genes.

Emerging issues with the current keratin-associated protein nomenclature.

Keratin associated proteins (KAPs) are a class of proteins that associate with keratin intermediate filament proteins through disulphide linkages to give fibres such as hair and wool their unique properties. Up to 90 proteins from some 25 families have been identified and this does not include polymorphic variants of individual proteins within these families. The existence of this diverse group of proteins has been known for some 75 years but, despite this, there is still no universally accepted nomenclature for them. This paper sets out the case for revising the current system to deal with this nomenclature issue.

Cytokeratin KRT8/18 expression differentiates distinct subtypes of grade 3 invasive ductal carcinoma of the breast.

Invasive ductal carcinomas of the breast (IDC) are routinely assessed on hematoxylin and eosin stained paraffin sections, with limited use of immunohistochemistry (IHC). Most IDC are regarded as a single diagnostic entity, IDC of no special type (IDC-NST), which is subdivided further only by grading. However, recent research suggests that there is high clinical relevance in differentiating IDC subtypes. Here, we ascertain whether tumor histology alone can predict basal or luminal cell phenotype in high-grade IDC-NST, and whether IHC and molecular characteristics are associated with the observed morphologies. A total of 29 grade 3 IDC-NST samples were studied, 10 tumors from a selected pilot cohort A and 19 tumors from an unselected validation cohort B. Along with histopathological assessment, the expression of ESR1, PGR, ERBB2 (HER-2), the basal/myoepithelial marker TP73L (p63), cytokeratins 5/6 (KRT5/6) and 14 (KRT14), and the luminal-specific cytokeratins 8/18 (KRT 8/18) and 19 (KRT19) was assessed by IHC. Hierarchical cluster analysis of clinicopathological variables and, separately, microarray expression profiles showed that the phenotypically distinctive basaloid and luminal tumors of cohort A fell into two main groups, defined by heterogeneous or uniformly positive expression of KRT8/18. The 38 genes differentially expressed between these two classes included ERBB2, KRT8, and six other genes previously associated with ERBB2-positive or luminal phenotypes. Tumor histology was not predictive for validation cohort B, but quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed two molecularly defined clusters that again aligned with the KRT8/18 staining phenotypes. Metaphase comparative genomic hybridization revealed 10q, 16q, and 20q copy-number imbalances that associated recurrently with KRT8/18 staining patterns.