Initial Steps in Creating a Patient-Centric Addendum to Clinical Trial Informed Consent Forms.

Introduction: The purpose of the informed consent form (ICF) is to outline the risks and benefits of an interventional clinical trial to potential participants. The aim of this study was to explore the feasibility of a short addendum to the ICF, summarizing key points most relevant to potential participants. Methods: A sample of 20 ICFs was reviewed against the requirements of the U.S. federal regulation documents and assessed for readability. Alongside the ICF review, we conducted focus groups and one-on-one interviews with people with lung cancer (n = 9) to learn what information was most important when considering participation in a clinical trial using a hypothetical phase 3 ICF. Results: The 20 ICFs reviewed were from phases 1 to 3, expanded-access, and single-patient trials covering predominantly NSCLC; 60% were global. The mean length of the ICFs was 21 (range: 15-34) pages. The average reading level was tenth grade whereas the average U.S. reading level was eighth grade. Readability varied by section, the "purpose of the study" section had the highest reading level. In the qualitative research component, participants were "overwhelmed" by the hypothetical ICF. Participants were also asked to list information for the addendum; their suggestions broadly map to federal regulations. An addendum with reference to sections in the ICF for additional details was well received. Conclusions: The variations in ICF architecture and readability make it difficult for patients to make an informed decision to participate in a clinical trial. Implications extend beyond lung cancer, highlighting key areas for ICF improvements and providing a roadmap for developing a patient-centric addendum.

Rectovaginal endometriosis with nodular smooth muscle metaplasia diagnosed via transrectal ultrasound-guided fine-needle aspiration cytology: An underused minimally invasive diagnostic technique?

Rectovaginal endometriosis is a severe variant of deeply infiltrating endometriosis. Laparoscopic assessment with tissue sampling remains the gold standard for diagnosis of endometriosis. However, transvaginal (TVUS) and transrectal ultrasound (TRUS) have been shown to be especially helpful in the diagnosis of deep endometriosis. We present the case of a 49-year-old female with menorrhagia, dysmenorrhea, and constipation. Upon pelvic examination, an incidental mass was palpated. A computed tomography (CT) scan revealed an anterior rectal wall mass and colonoscopy was non-diagnostic. Further work-up with MRI showed a 3.9 cm mass centered within the upper rectovaginal septum. TRUS guided fine-needle aspiration (TRUS-FNA) revealed cohesive epithelial cell groups without significant cytologic atypia and a second population of bland spindle cells. Cell block slides showed glandular epithelium with associated stroma that exhibited endometrial morphology and immunophenotype. Nodular fragments of spindle cells with smooth muscle immunophenotype and fibrosis were also present. The overall morphologic findings were consistent with rectovaginal endometriosis with nodular smooth muscle metaplasia. Medical management with nonsteroidal aromatase inhibitor with radiologic follow-up was selected. Rectovaginal endometriosis represents a type of deep endometriosis usually associated with severe pelvic symptoms. Metaplastic smooth muscle cells are a frequent component of endometriosis in the rectovaginal pouch with nodular growth and may present diagnostic challenges. TRUS-FNA is a minimally invasive procedure that can provide an accurate diagnosis of endometriosis, even in this variant of deep infiltrating disease.

Contemporary evaluation of estrogen receptor and progesterone receptor expression in breast cancer-associated stroma.

PURPOSE: To investigate nuclear estrogen receptor α (ERα) and progesterone receptor (PR) immunohistochemistry (IHC) patterns in the stroma surrounding invasive carcinoma and assess associations with clinicopathologic features. METHODS: A retrospective database search (1/2017-12/2020) identified breast core biopsies with invasive carcinoma. ERα/PR IHC expression in invasive carcinoma and stromal cells was categorized visually as positive (> 10%), low positive (1-10%) or negative (< 1%). Tumors were divided into 4 subtypes by IHC: Luminal, Luminal HER2, HER2 enriched, and triple negative. Clinicopathologic features associated (univariate p-value < 0.15) with ERα/PR stromal expression were investigated further using stepwise multivariable logistic regression. RESULTS: Of 1512 biopsies, 1278 had accessible IHC. 55.6% (711/1278) and 10.4% (133/1274) of cases showed cancer-associated stromal fibroblast expression of ERα and PR, respectively. Stromal ER positivity was significantly associated with use of the Ventana (with SP1 clone) versus Leica (with 6F11 clone) platform and in cases with Luminal cancer subtype. PR stromal expression was significantly associated with Luminal subtype, obesity, and younger age. CONCLUSIONS: Expression of ERα and PR in breast cancer-associated stroma showed associations that suggest both biologic and analytic influence. Reproducible expression patterns may inform expansion of ERα/PR guidelines for the assessment of internal controls.

Unveiling the histopathologic spectrum of MRI-guided breast biopsies: an institutional pathological-radiological correlation.

PURPOSE: Breast magnetic resonance imaging (MRI) has high sensitivity but suffers from low specificity, resulting in many benign breast biopsies for MRI-detected lesions. We sought to compare histologic findings between patients who underwent MRI-guided breast biopsy versus biopsy via other imaging modalities as well as to examine features associated with malignancy in the MRI cohort to help inform MRI-biopsy practice. METHODS: A 2-year (2018-2019) retrospective review of breast biopsies at our enterprise was conducted. Biopsies were categorized as stereotactic, ultrasound, MRI, or palpation guided. Pathology was categorized as benign (further divided into nine categories), atypical, or malignant (subdivided into in situ and invasive carcinoma). Pathology was compared between biopsy groups. Clinical, pathologic, and imaging features were compared between pathology groups within the MRI cohort. RESULTS: 5828 biopsies from 4154 patients were reviewed, including 548 MRI-guided biopsies with stratification of MRI-biopsy pathology as follows: 69% benign, 13.8% atypical, and 17.2% malignant. Among benign MRI biopsies, there was higher frequency of "clustered cysts with papillary apocrine metaplasia" (56/548; 10.2%) and lower rate of fibroadenoma/fibroadenomatous change (55/548; 10%) compared to other modalities (158 or 3% and 1144 or 21.7% of 5280 biopsies, respectively). Multivariate analysis revealed indication of breast cancer (p < .0001), ipsilateral cancer (p < .0001) and rapid initial phase kinetics (p = .017) to remain significantly associated with malignant MRI-biopsy pathology. CONCLUSIONS: A concurrent or recent breast cancer diagnosis was most predictive of malignancy on MRI-guided breast biopsy. Combined MRI feature evaluation and radiologic-pathologic concordance activities may allow for prognostic refinement and improved risk stratification.