Venous Thromboembolism in Peritoneal Mesothelioma: Uncovering the Hidden Risk.

INTRODUCTION: Venous thromboembolism (VTE) is a common complication in patients with abdominal malignancies. Despite known associations between pleural mesothelioma and increased VTE risk, the characteristics of VTE in patients with peritoneal mesothelioma (PeM) remain undescribed. METHODS: Patients treated for PeM were retrospectively identified from our institutional database. The frequency of VTE was assessed and logistic regression modeling was employed to assess VTE risk factors. The association between VTE and overall survival was also ascertained. Recommended thromboprophylaxis for patients who underwent surgery at our institution comprised a single preoperative dose of prophylactic anticoagulation, followed by daily dosing for four weeks postoperatively. RESULTS: Among 120 PeM patients, 26 (21.7%) experienced VTE, including 19/91 (20.9%) surgical patients, 4/23 (17.4%) patients who received systemic therapy, and 3/6 (50%) patients who underwent observation (p = 0.21). Most events were symptomatic (n = 16, 62%) and were attributable to pulmonary emboli (n = 16, 62%). The 90-day postoperative VTE rate was 4.4% (4/91), including 1 of 60 patients who underwent index surgical intervention at our institution and 3 patients with surgery elsewhere. A low serum albumin concentration was associated with VTE in non-surgical patients (odds ratio 0.12, confidence interval [CI] 0.02-0.72; p = 0.03). No significant difference in overall survival was observed between patients with and without VTE (median 46.0 months [CI 24.9-67.0] vs. 55.0 months [CI 27.5-82.5]; hazard ratio 0.98 [CI 0.54-1.81], p = 0.98). CONCLUSIONS: A high risk of VTE was observed in PeM patients, warranting suspicion throughout the disease trajectory. Postoperative VTE rates were within acceptable limits with 4-week thromboprophylaxis.

Role of Tumor-informed Personalized Circulating Tumor DNA Assay in Informing Recurrence in Patients With Peritoneal Metastases From Colorectal and High-grade Appendix Cancer Undergoing Curative-intent Surgery.

OBJECTIVE: To investigate the role of a personalized, tumor-informed circulating tumor DNA (ctDNA) assay in informing recurrence in patients with peritoneal metastases (PM) from colorectal (CRC) and high-grade appendix (HGA) cancer after curative cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC). BACKGROUND: Over 50% of patients with CRC/HGA-PM recur after optimal CRS-HIPEC. The limited sensitivity of axial imaging and diagnostic biomarkers is a significant cause of delay in the detection of recurrence and initiation of further therapies. Plasma ctDNA has a promising role in monitoring response to treatment and/or recurrence after primary cancer resection. METHODS: Patients with CRC/HGA-PM who underwent curative CRS-HIPEC and serial postresection ctDNA assessments were included. Patients with rising postoperative ctDNA levels were compared with those with stable, undetectable ctDNA levels. Primary outcomes were the percentage of patients with recurrence and disease-free survival (DFS). Secondary outcomes were overall survival, ctDNA sensitivity, lead time, and performance of ctDNA compared with carcinoembryonic antigen. RESULTS: One hundred thirty serial postresection ctDNA assessments [median 4, interquartile range (IQR), 3 to 5] were performed in 33 patients (n = 13 CRC, n = 20 HGA) who underwent completeness of cytoreduction-0/1 CRS with a median follow-up of 13 months. Of the 19 patients with rising ctDNA levels, 90% recurred versus 21% in the stable ctDNA group (n = 14, < 0.001). Median DFS in the rising ctDNA cohort was 11 months (IQR, 6 to 12) and not reached in the stable ( P = 0.01). A rising ctDNA level was the most significant factor associated with DFS (hazard ratio: 3.67, 95% CI: 1.06-12.66, P = 0.03). The sensitivity and specificity of rising ctDNA levels in predicting recurrence were 85% and 84.6%, respectively. The median ctDNA lead time was 3 months (IQR, 1 to 4). Carcinoembryonic antigen was less sensitive (50%) than ctDNA. CONCLUSIONS: This study supports the clinical validity of serial ctDNA assessment as a strong prognostic biomarker in informing recurrence in patients with CRC/HGA-PM undergoing curative resection. It also holds promises for informing future clinical trial designs and further research.

Spanish Adaptation and Evaluation of Clinical Discussion Guides: Communicating the External Beam Radiotherapy Experience (CEBRE) en Español.

PURPOSE: Cancer is the leading cause of death for the Hispanic/Latinx United States (US) community, which comprises 64% of the US population with limited English proficiency. Despite the common use of radiation therapy for cancer treatment, there is a dearth of radiation therapy educational materials-at appropriate reading levels-available in Spanish. To address the gap in patient-centered educational resources for communicating with Spanish-speaking patients about radiation therapy, we sought to linguistically and culturally adapt the Communicating the External Beam Radiotherapy Experience (CEBRE) clinical discussion guide series into Spanish. METHODS AND MATERIALS: From January to December 2021, we developed and applied a stepwise methodology for Spanish adaptation of the discussion guides involving (1) professional translation; (2) interprofessional review for linguistic and cultural appropriateness and medical accuracy; (3) design review; and (4) evaluation for readability, understandability, and actionability using validated tools. We applied 4 indices for readability evaluation: Gilliam-Peña-Mountain, Läsbarhetsindex, Rate Index, and the Spanish Simple Measure of Gobbledygook. Two trained reviewers assessed understandability and actionability using the Patient Education Materials Assessment Tool. RESULTS: After 2 revision rounds, 4 CEBRE en español discussion guides were produced through an interprofessional, iterative translation and linguistic/cultural adaptation process. Readability scores across the 4 guides ranged from 4.3 to 7.3 grade-level equivalents, thereby meeting the American Medical Association's 8th-grade standard. Patient Education Materials Assessment Tool analysis yielded near-perfect scores along understandability and actionability domains. CONCLUSIONS: The stepwise linguistic/cultural adaptation process yielded a patient-centered guide that is appropriately readable, understandable, and actionable for Spanish-speaking patients receiving radiation therapy in the US. Future work should include an external evaluation of CEBRE en español by clinicians and patients. The methodology described can be applied to adapting resources for patient-centered communication in other fields of medicine and into other languages as part of an interprofessional approach to delivering equitable health care for all.

Exploring the Impact of Language Concordance on Cancer Communication.

PURPOSE: Patients with cancer who have limited English proficiency are more likely to experience inequities in cancer knowledge, timely care, and access to clinical trials. Matching patients with language-concordant clinicians and working with professional interpreters can effectively reduce language-related disparities, but little data are available regarding the impact of language-concordant interactions in oncology care. This study aimed to assess the use of the Roter Interaction Analysis System (RIAS) in language-concordant and -discordant interactions for patients with non-English language preference presenting for an initial oncology visit at four New York City hospitals. METHODS: We used the RIAS, a validated tool for qualitative coding and quantitative analysis, to evaluate interactions between 34 patients and 16 clinicians. The pairings were stratified into dyads: English language-concordant (n = 12); professionally interpreted (n = 11); partially language-concordant (n = 4, partially bilingual clinicians who communicated in Spanish and/or used ad hoc interpreters); and Spanish language-concordant (n = 7). A trained Spanish-speaking coder analyzed the recordings using established RIAS codes. RESULTS: Spanish language-concordant clinicians had almost two-fold greater number of statements about biomedical information than English language-concordant clinicians. Spanish language-concordant patients had a higher tendency to engage in positive talk such as expressing agreement. The number of partnership/facilitation-related statements was equivalent for English and Spanish language-concordant groups but lower in professionally interpreted and partially language-concordant dyads. CONCLUSION: Language concordance may facilitate more effective biomedical counseling and therapeutic relationships between oncology clinicians and patients. Future research should further explore the impact of language concordance on cancer-specific health outcomes.

Contribution of promoter DNA sequence to heterochromatin formation velocity and memory of gene repression in mouse embryo fibroblasts.

Durable gene silencing through the formation of compact heterochromatin domains plays a critical role during mammalian development in establishing defined tissues capable of retaining cellular identity. Hallmarks of heterochromatin gene repression are the binding of heterochromatin protein 1 (HP1), trimethylation of lysine 9 on histone H3 (H3K9me3) and the methylation of cytosine residues of DNA. HP1 binds directly to the H3K9me3 histone modification, and while DNA methyltransferases have been found in complex with histone methyltransferases and HP1, there remains much to be known about the relationship between DNA sequence and HP1 in differentiated mammalian cells. To further explore this interplay in a controlled system, we designed a system to test the effect of promoter CpG content on the formation kinetics and memory of an HP1-mediated heterochromatin domain in mouse embryo fibroblasts (MEF)s. To do this, we have constructed a side-by-side comparison of wild-type (CpGFull) and CpG-depleted (CpGDep) promoter-driven reporter constructs in the context of the Chromatin in vivo Assay (CiA), which uses chemically-induced proximity (CIP) to tether the chromoshadow domain of HP1α (csHP1α) to a fluorescent reporter gene in a reversible, chemically-dependent manner. By comparing the response of CpGFull and CpGDep reporter constructs, we discovered that the heterochromatin formation by recruitment of csHP1α is unaffected by the underlying CpG dinucleotide content of the promoter, as measured by the velocity of gene silencing or enrichment of H3K9me3 at the silenced gene. However, recovery from long-term silencing is measurably faster in the CpG-depleted reporter lines. These data provide evidence that the stability of the HP1 heterochromatin domain is reliant on the underlying DNA sequence. Moreover, these cell lines represent a new modular system with which to study the effect of the underlying DNA sequences on the efficacy of epigenetic modifiers.