tbuckley/cabot-search huggingface dataset:
Assessing our adherence to bone protection standards in metastatic prostate cancer in the largest Irish center: Are we falling behind?
Authors: Razia Aslam, Danial Hadi, Syed Muhammad Bilal Shah, Emma Barron
Journal: Journal of Clinical Oncology (2024)

e24145 Background: Prostate cancer ranks as the second most prevalent cancer in men globally, often necessitating androgen deprivation therapy (ADT) as part of its treatment. While ADT effectively diminishes testosterone levels, a vital factor in prostate cancer cell growth, it concurrently poses a notable side effect – an accelerated rate of bone loss. This heightened bone loss elevates the vulnerability of patients to osteoporosis and fractures. The optimization of bone health entails early identification of patients susceptible to osteoporosis and fractures, the implementation of preventative measures, and prompt interventions to mitigate bone loss and fracture risks. Methods: The audit aims to evaluate adherence to established guidelines, such as those outlined by the National Comprehensive Cancer Network (NCCN) and the European Society for Medical Oncology (ESMO), concerning the assessment and optimization of bone health. A retrospective analysis was performed on the medical records of prostate cancer patients who underwent Androgen Deprivation Therapy (ADT) at St James Hospital in Dublin. Pertinent data, encompassing patient demographics, duration of ADT, documentation of bone health assessment, frequency of Bone Mineral Density (BMD) testing, utilization of preventive measures (e.g., calcium and vitamin D supplementation), and any interventions for bone health optimization (such as bisphosphonate therapy and denosumab), was systematically collected. Results: A comprehensive review encompassed 57 patients, revealing that 38 patients (67%) exhibited metastatic disease. Among them, 42 patients (74%) presented with castrate-sensitive disease. Out of the total, 24 patients (42%) underwent a baseline Dual-Energy X-ray Absorptiometry (DEXA) scan. Results indicated that 12 patients were diagnosed with Osteoporosis, 9 with Osteopenia, and 3 with normal Bone Mineral Density (BMD). At baseline, 26 patients (46%) initiated Calcium and Vitamin D supplements, while 12 patients (21%) commenced Bisphosphonates/Denosumab based on DEXA scan outcomes. Notably, 8 (14%) patients experienced a skeletal/bone-related event which is much higher than reported in literature. Conclusions: The findings are intended to guide healthcare professionals in optimizing bone health strategies, with the ultimate goal of improving patients' quality of life and minimizing the risk of fractures and related complications. Identified areas for improvement in clinical practices will be addressed by implementing recommended recommendations, aiming to enhance patient care, decrease the risk of osteoporosis and fractures, and overall improve patient outcomes. A re-audit is planned to monitor ongoing adherence to guidelines and assess the impact of interventions implemented as a result of this study.
The clinical utility of the 90-gene expression assay on diagnosis and management in patients with cancer of unknown or unclear primary.
Authors: Peng Qi, Yifeng Sun, Qinghua Xu, Qifeng Wang, Xiaoyan Zhou
Journal: Journal of Clinical Oncology (2024)

e15172 Background: The diagnosis and management of patients with cancer of unknown or unclear primary present significant clinical hurdles, often culminating in unfavorable outcomes. A randomized phase III trial (CUP001) has demonstrated that site-specific treatment guided by the 90-gene-expression assay (Canhelp-Origin Assay) resulted in more therapy options, and significantly improved progression-free survival compared with empirical chemotherapy in patients with cancer of unknown primary. This study evaluated the clinical utility of the 90-gene expression assay in the diagnosis and management of patients with cancer of unknown or unclear primary. Methods: Patients who underwent the 90-gene expression assay at Fudan University Shanghai Cancer Center (FUSCC) between February 2023 and December 2023 were enrolled in the study. Data collection encompassed patient demographics, clinical characteristics, and pathological features. Results: Patient enrollment began in February 2023 and closed in December 2023 after enrolling 303 patients with 51 inpatient cases and 244 pathological consultation cases (from 144 sites). Among them, 295 patients met all inclusion criteria, yielding an overall success rate of 97.4% (295/303). Tumor cells were enriched by either macrodissection (N = 257) or microdissection (N = 38), with median highest similarity scores of 57.5 and 67.1, respectively. Using a positive cutoff value of the highest similarity score ≥45.3, the positivity rates for macrodissection and microdissection were 66.5% (171/257) and 81.6% (31/38), respectively. Of the enrolled patients, 177 (60%) were male, and 118 (40%) were female, with a median age of 63 years (range: 25 to 85 years). Predictive results encompassed 21 tumor types, with the most common being gastroesophageal cancer (N = 40, 13.6%), lung cancer (N = 37, 12.5%), breast cancer (N = 36, 12.2%), head and neck squamous cell carcinoma (N = 29, 9.8%), and ovarian cancer (N = 28, 9.5%). Of 166 samples with an assigned grade, 89.8% were poorly differentiated or undifferentiated, 6.0% were moderately differentiated, and 4.2% were well differentiated. The consistency of prediction results and clinicopathological results will be further evaluated after follow-up. Conclusions: This study demonstrates that the 90-gene expression assay has diagnostic implications for patients with cancer of unknown or unclear primary. This affirms its clinical utility as a standard diagnostic approach in the diagnosis and management of these patients, facilitating the formulation of more precise treatment strategies and ultimately enhancing prognosis.
Enabling accessibility to the CellScape spatial biology workflow for researchers using standard histology protocols and pre-slided specimens.
Authors: Benton Berigan, Oliver Braubach, Matthew Ingalls, Xenia Meshik, J. Spencer Schwarz, Kayla Cashion, Adam Northcutt, Charles Jackson
Journal: Journal of Clinical Oncology (2024)

e15185 Background: Solid tumor specimen collection during clinical trials often follows a standard histology protocol, ending in the generation of FFPE sections mounted onto 1 mm histology slides. Though a common sample format for researchers developing tissue-based biomarkers, slides present a data quality challenge for multiplexed spatial biology workflows. Here we present data describing an innovative flow cell design fully compatible with pre-slided tissue specimens. We collected spatial biology data using this slide-compatible flow cell and compared it to the gold standard direct mounting on coverglass. Several rounds of marker staining and imaging demonstrate equivalency in method outcomes including image resolution, signal to noise, and re-interrogation capacity. Methods: FFPE biopsy tissue specimens (tumor punch biopsies and a tonsil section) were mounted on standard histology slides. These specimens were incorporated into flow cells using a new glass coverslip and porting device, CellScape™ Slide, that pairs with a standard histology slide to form a microfluidic chamber. After mounting, each sample was probed for consensus CD markers (CD45, CD3, CD4,CD8,CD20, etc.) through several rounds of iterative immunofluorescence staining using CellScape™ Precise Spatial Multiplexing. The resulting multi-layered whole slide image dataset was then interrogated for spatial resolution and signal-to-noise using digital image analysis. Results: Spatial resolution and signal-to-noise ratio (SNR) were assessed through comparison to data collected from similar samples using the existing CellScape microfluidic chip. The lowest intensity signal collected with at least a 30:1 SNR (acceptable for image analysis) was equivalent or lower in the CellScape Slide preparation (equivalent sensitivity). The highest intensity signal collected was equivalent between the two flow cell designs. Comparing stain quality (specificity, sensitivity) among markers stained through multiple rounds of iterative staining, imaging, and signal remove via photoinactivation showed that the CellScape Slide flow cell is on par with or better than the existing CellScape chip. Further, the usable clear window of the CellScape Slide flow chamber, measuring 16 mm x 44 mm, was found to be greater than twice that of the existing chip. Literature review determined this to also be the largest imaging window available among commercially available spatial biology platforms. Conclusions: Assessment of the CellScape Slide flow cell, innovative in providing access to the CellScape spatial biology workflow for pre-mounted FFPE tissue, determined that the optical performance of the new flow cell is at least on par with the existing flow cell. Further, the usable window is over twice the area, and the new flow cell is fully capable of supporting re-interrogation of the sample.
Evaluation of biomarkers of response in patients with breast cancer with <i>BRCA</i> 1/2 pathogenic variants treated with PARP inhibitors.
Authors: Fatma Nihan Akkoc Mustafayev, Angelica M. Gutierrez, Mark F. Munsell, Junjie Chen, Katharina Schlacher, John A. Tainer, Constance T. Albarracin, Banu Arun
Journal: Journal of Clinical Oncology (2024)

e15188 Background: Several prospective studies highlight the pivotal role of PARP inhibitors (PARPi) in treating BRCA-associated breast cancers (BC), demonstrating a significant overall response rate (ORR) of up to 60% in advanced BC patients with BRCA 1/2 germline pathogenic variants (PV). Despite their clinical efficacy, the factors predicting PARPi response, the mechanisms of resistance to PARPi, and the clinical strategies to overcome these challenges are still unknown. The aim of this study is to establish tissue microarrays (TMA) from primary breast tumor tissue from BC patients with BRCA1/2 PVs who were treated with PARPi and identify biomarkers of PARPi resistance. Methods: Stage 4 BC patients with BRCA 1/2 PVs who presented to the University of Texas MD Anderson Cancer Center Breast Medical Oncology clinics and were treated with PARPi between 2008-2023 were identified using our database. Available patient tissue samples were obtained from institutional tumor banks. TMA from breast tumor tissue created and evaluated by our collabrating pathologists for expression of biomarkers:Wee-1, MRE, BP1,and c-Myc. Clinical and tumor characteristics analyzed included:Age at diagnosis, treatment details, tumor characteristics including histological type, hormonal receptor status, Her-2/Neu status, grade, Ki-67 and clinical outcome. Descriptive statistics, the Fisher exact test, and the log rank test were used to report patient characteristics and outcomes. Here we report on initial TMA construct and biomarker analysis. Results: So far TMA from 12 patients treated with PARPi were succesfully constructed. Patient characteristics include: Median age of 36.5 years (29-57). Nine (75%) and 3 (25%) patients had BRCA1 and BRCA2 mutations, respectively. All patients had invasive ductal carcinoma and 9 (75%) had triple negative BC. Most patient (75%) had high nuclear grade BC and median Ki-67 was 75 (15-90). In 11 evaluable patients, the ORR was 72.7%. The median OS was 383.6 months (95% CI 62.5-383.6) and median PFS was 31.5 months (95% CI 10.8-NE). No significant difference in biomarker expression was observed between PARPi-responders and non-responders (Table1). Conclusions: This report presents unique data on novel predictive biomarkers of response and evaluates the evidence for potential biomarkers. Further analysis on a larger TMA cohort is ongoing. [Table: see text]
Comparison of infective endocarditis in patients with and without malignancy: A propensity score matched analysis.
Authors: Soe Winn, Sajog Kansakar, Shreeja Shikhrakar, Ashish Guragain, Dilichukwu Chudy-Onwugaje
Journal: Journal of Clinical Oncology (2024)

e24030 Background: Cancer patients are at a higher risk of infective endocarditis (IE) due to immunosuppressed state, indwelling catheters and recurrent infections. Due to the clinical scenario being relatively uncommon, there is lack of real-world data on prevalence, trends and outcomes of IE in cancer patients. Methods: We extracted data from the National Inpatient Sample (NIS) Database from 2016 to 2020. We included all admissions ≥18 years old with a principal diagnosis of IE with and without a cancer diagnosis using International Classification of Diseases Tenth Revision (ICD-10) codes. Propensity score matching was performed to balance hospital characteristics, patient demographics and comorbidities between the two groups. Univariate logistic regression was performed in the balanced cohorts. The primary outcome was inpatient mortality. Analysis was performed using STATA-MP, version 14.2. Results: A total of 70,225 admissions for IE were identified between 2016-2020, of which 2,294 (3.27%) had a history or active cancer. The annual number of admissions for IE did not show a significant change (p trend = 0.56); however, the proportion of IE patients with cancer doubled from 2.33% to 4.61% (p trend &lt; 0.01) over the study period. After propensity score matching, there was no significant difference in in-hospital mortality (odds ratio [OR] 1.30, 95% CI 0.79-2.16, p = 0.31) between IE patients with and without cancer. Cohort with cancer had lower odds of experiencing respiratory failure (OR 0.52, 95% CI 0.33-0.83, p &lt; 0.01) and stroke (OR 0.35, 95% CI 0.25-0.49, p &lt; 0.01), although venous thromboembolism was more common in cohort with cancer (OR 3.03, 95% CI 1.76-5.21, p &lt; 0.01). There was no difference in acute kidney injury or shock between the two groups. Cohort with cancer was less likely to undergo valve replacement surgery (OR 0.42, 95% CI 0.31-1.24, p &lt; 0.01). The median length of stay (11 days vs 14 days, p &lt; 0.01) and hospital charges ($70,698 vs $86,763, p &lt; 0.01) were higher in the cohort without cancer. Conclusions: Underlying cancer was seen in growing proportion of admissions for IE over the study period. The pattern of complications was different between patients with and without cancer, which underscores the importance of cancer history in management of IE. Although there was no difference in mortality between patients with and without cancer, patients with cancer were less likely to undergo valve replacement surgery during the admission. Further research is needed to explore the specific factors influencing treatment decisions and long-term outcomes in cancer patients with IE.
Genomic analysis of the tumor microenvironment in Asian and Native Hawaiian and Pacific Islander patients with triple negative breast cancer.
Authors: Edward Nguyen, Shirley Cheng, Connie Chang, Ba Thong Nguyen, Vedbar Khadka, Youping Deng, Jeffrey Killeen, Jami Aya Fukui
Journal: Journal of Clinical Oncology (2024)

e12644 Background: Triple negative breast cancer (TNBC) accounts for approximately 10- 20% of breast cancer cases and has the worst overall survival and prognosis compared to other subtypes. Unlike other subtypes, patients with TNBC are responsive to neoadjuvant therapy. A higher percent of stromal tumor infiltrating lymophocytes (sTILs) in the tumor microenvironment of TNBC correlates with an improved prognosis. Previous studies demonstrate that Native Hawaiians and Pacific Islanders (NHPIs) and Asians have equivocal percent of sTILs. Yet NHPIs have a higher mortality rate at 24.9% compared to Asians at 11%. Our study aims to molecularly characterize the tumor microenvironment in a diverse population of patients with TNBC who received neoadjuvant therapy. Methods: Retrospective chart review was conducted on 12 Asians and 12 NHPI patients with early stage TNBC from 2015 to 2022 from a medical oncology clinic within the Hawai’i Pacific Health system. Patient data collected include age at diagnosis of breast cancer, histology, BMI, clinical stage, sTILs, residual cancer burden, neoadjuvant treatment, and pathologic complete response. Core biopsy samples were processed and analyzed using the nCounter Breast Cancer 360 Panel. Further analysis was obtained using the nSolver Advanced Analysis Module. Results: Patient characteristics are listed in the table. Most patients had the basal-like immunosuppressed TNBC subtype. Among differentially expressed genes between races, 31 genes were statistically significant. NHPIs expressed more IL12RB2 and MYC, and Asians expressed more FGFR4 and MLPH. Among responders compared to non-responders, 5 genes were statistically significant. Responders expressed more STC1 and PTGER3, and non-responders expressed more CRAYAB, TMPRSS2, and CHAD. Among old and young patients, 132 genes were statistically significant. Older patients expressed more FUT3 and CKMT1, and younger patients expressed more MMP7 and MIA. Conclusions: In this pilot study, the molecular and genetic differences suggest that the tumor microenvironment may play a role in treatment outcomes between NHPIs and Asians. Further analysis will be conducted to determine the differences in immune cell infiltration. [Table: see text]
Survival outcome prediction of breast carcinomas on whole-slide histopathology images using deep learning.
Authors: Julian Paul, Céline Bossard, Joseph Rynkiewicz, Florence Molinié, Sanae Salhi, Jean-Sebastien Frenel, Yahia Salhi, Jérôme Chetritt
Journal: Journal of Clinical Oncology (2024)

1070 Background: Breast cancer is the most common cancer among women with 2 million new cases and 627,000 deaths in 2020. Early diagnosis and effective treatment are crucial for improved outcomes. Prognosis mainly depends on histopathological features, among them grade. As whole slide histopathology image (WSI) of tumor tissue contains a huge amount of hidden morphological features unexploited by pathologists, we investigate the potential of Artificial Intelligence (AI)-based analysis on WSI to predict prognosis in terms of 5-year overall survival in breast cancer patients. Methods: We used a novel deep neural network (DNN), DiaDeepBreastPRS, designed specifically for predicting a survival risk score in breast cancer patients based on H&amp;E-stained whole slide images (WSI) of tumor tissues. The model incorporates two distinct viewpoints, one capturing cellular details and the other the tissue-level information. DiaDeepBreastPRS was trained and evaluated on a multi-centric discovery cohort of 1,027 patients (1,095 H&amp;E WSI) from the TCGA-BRCA dataset using a cross-testing and cross-validation technique. It was evaluated on an external cohort, comprising 232 patients (247 H&amp;E WSI). A statistical analysis with a multivariate Cox regression model was carried out on clinico-pathological data. AI scores and the concordance index (c-index) serves as the metric for assessing the performance. The predicted risk scores were used for effective risk stratification of breast carcinomas. Results: On the TCGA-BRCA dataset, the model achieved an average c-index of 67%, which reaches 78% by adding the pTNM stage and age at diagnosis. On the external dataset, the model achieved a c-index of 66% and 75% when including some histopathological prognosis factors (pTNM stage, age at diagnosis, HER2 and HR status and mitosis). The AI score was independently associated with the survival of breast cancer patients with the highest hazard ratio (HR 2.46, p&lt;0.005). Furthermore, the model was able to significantly discriminate between the 2 groups of patients, with a good and a poor prognosis in terms of overall survival (p&lt;0.005). Conclusions: In this study, we showcased that the algorithm was able to instantly extract prognostic morphological features from H&amp;E whole slide images (WSI) and could be included in the pathology report. This could potentially enhance clinical decision-making, elevating the standard of care. Compared to commonly used molecular signatures, the AI algorithm enables a reduction in response time and cost savings. However, further investigations using additional independent cohorts are essential to consolidate the algorithm's performance and allow its generalizability, establish its superiority over existing prognostic markers, and provide insights into its interpretability.
A qualitative analysis on the awareness of surrogacy as an alternative parenting option for people diagnosed with cancer.
Authors: Alexa M. Steckler, Don S. Dizon, Camille Higel-Mcgovern, Christine Mary Duffy
Journal: Journal of Clinical Oncology (2024)

e24097 Background: ASCO guidelines recommend counseling about the impact of cancer treatment on fertility, preservation options, and referral to a reproductive specialist when indicated. However, other family-building options, such as surrogacy have not been specifically included in the guidance. Very little has been reported on counseling and use of surrogacy among people treated for cancer despite it being a viable option for parenthood in those with cancer-induced infertility. Objective: The Counseling and Use of Surrogacy Among Cancer Survivors (CUSACS) is aimed to be the first nationwide survey to examine the proportion of patients who received surrogacy information as part of fertility counseling at diagnosis, as well as interest and participation in surrogacy. As part of survey development, we conducted qualitative interviews and here, we report the thematic analysis from those conversations. Methods: We created an internet-based REDCap survey on fertility and surrogacy counseling and vetted it with four national cancer organizations: Young Survival Coalition (YSC), Cervivor, the Chick Mission, and For the Breast of Us. We conducted 17 survivor interviews from these organizations focusing on survey content, language, and usability. Authors analyzed interview transcripts separately and through consensus. Results: Three major themes emerged with representative quotes in Table 1: Identity, Self-sufficiency, and Regret. Iterative changes were made to the survey to incorporate feedback. Conclusions: Survivor interviews provided insight into important themes regarding fertility and surrogacy counseling. Our survey will be distributed through the partnering organizations and will be the first national survey to explore surrogacy counseling at cancer diagnosis. [Table: see text]