tbuckley/cabot-search huggingface dataset:
Analysis of effectiveness of FLOT perioperative chemotherapy in resectable locally advanced gastric or esophago-gastric junction cancer in a Kazakhstani population.
Authors: Altay Kerimkulov, Tomiris Sarina, Talgat Uskenbayev, Bayduysen Usipbekov, Bakhtzhan Umerzakova, Dina Kovalchuk, Aigerim Sipenova
Journal: Journal of Clinical Oncology (2024)

e16129 Background: Gastric cancer is the third most common malignancy in Kazakhstan and the second leading cause of cancer-related mortality. Docetaxel, oxaliplatin, leucovorin, and 5-fluorouracil (FLOT) perioperative chemotherapy is widely accepted treatment strategy of locally advanced gastric adenocarcinoma in Western countries. However, radical surgery is a preferable approach in Kazakhstan. The objective of this study was to assess the effectiveness and feasibility of FLOT perioperative chemotherapy in curable locally advanced gastric or esophago-gastric junction cancer. Methods: In this study, we reviewed the retrospective data of patients with locally advanced gastric or esophago-gastric junction cancer, who received FLOT perioperative chemotherapy between January 2020 and December 2022 in single center. To evaluate the effectiveness of treatment, histopathological regression, disease free survival (DFS) and 1- and 3-year overall survival outcomes were analyzed. Results: Total 136 patients with stage II and III with gastric or esophago-gastric junction cancer were treated. Fifty-six patients (41%) received FLOT preoperative chemotherapy. 9% (5) patients couldn’t complete all cycles of chemotherapy due to serious adverse events. Disease progression was observed in 10 (19%) patients after FLOT preoperative chemotherapy. Of the 46 radically operated patients, 5 (11%) had complete or near complete pathology response, 33 (72%) patients had partial response, and 8 (17%) patients had no response for preoperative chemotherapy (p = 0,405). 7 patients had not get adjuvant chemotherapy. Overall, 1- and 3-year survival were 78,6% and 34,9% respectively, disease free survival was 76,8% and 39% respectively. Conclusions: The FLOT perioperative chemotherapy was effective and feasible to administer and might be a standard treatment option among patients with locally advanced gastric or esophago-gastric junction cancer.
Convolutional neural network and glioma genotyping: A systematic review.
Authors: Hamidreza Ashayeri, Mirsaeed Abdollahi, Ali Jafarizadeh, Soroush Morsali, Siamak Pedrammehr, Roohallah Alizadehsani, Juan Manuel Gorriz Saez
Journal: Journal of Clinical Oncology (2024)

e14038 Background: Gliomas are the most common primary intracranial tumors. Overall, there are 23 different glioma types, and the grading and prognosis of each type are determined by their specific mutations. Several identified mutations are IDH gene status, CDKN2A/B homozygote delegation, PTEN mutation, p53 mutation, TERT promotor mutation, H3K27M mutation, MGMT promotor methylation, trisomy 7/monozomy10, EGFR amplification, ATRX mutation, 1p/19q codeletion, and BRAF mutation. These specific mutations and genomic features can have their distinctive radiologic features seen in different magnetic resonance imaging (MRI) sequences. By using a Convolutional Neural Network (CNN) for feature extraction, the genotyping power of MRI for glioma could be increased. To address this, we systematically reviewed the use of different CNN-based models to detect the genetic context of glioma based on the MRI images. Methods: We conducted a systematic search in PubMed, Embase, Scopus, Web of Science, and Google Scholar. We included original peer-reviewed human studies (retrospective or prospective), focusing on the use of CNN in individuals with glioma. We excluded animal studies, studies with no CNN-based models, reviews, book chapters, conference abstracts, and case reports. JBI checklists were utilized for quality assessment. Results: The initial search resulted in 973 articles. after removing duplicates, 563 studies entered the screening process by title and abstract. 59 studies met our inclusion criteria (56 retrospective and 3 prospective cohort studies) with a total of 26434 glioma patients included (studies ranged from 21 – 2648 individuals). 31 studies used CNN methods only in different stages of image processing (tumor segmentation, feature extraction, image encoder) and 28 studies used CNN as a classifier and mutation predictor. ResNet was the most commonly used CNN-based model (n = 14). U-net (n = 7) and DenseNet models (n = 4) were other commonly used CNN-based models. Included studies targeted IDH status (n=44), 1p/19q codeletion (n=18), MGMT promotor methylation (n=11), ATRX mutation (n=5), TERT promotor mutation (n=5), CDKN2A/B homozygote deletion (n=3), PTEN mutation (n=3), p53 mutation (n=3), H3K27M mutation (n=2), trisomy 7/monozomy10 (n=2), EGFR amplification (n=2), and BRAF mutation (n=1). Highly severe methodological heterogeneity among these studies excluded the possibility of meta-analysis. Conclusions: Current studies have shown that, as a non-invasive method, using CNN-based models on multiple MRI sequences increases the power of early detection and prediction of glioma genetic types before pathological confirmation and has promising results. However, DL performance varies among mutations. Combining multiple DL models with clinical and radiomic features in different and larger databases can further increase the final results.
Real-world comparison: Neoadjuvant pembrolizumab (pembro-NACT) vs. dose-dense neoadjuvant chemotherapy (ddNACT) in early stage triple-negative breast cancer (TNBC).
Authors: Mali Barbi, Jovanka Noel, Chung-Shien Lee, Husneara Rahman, Kit Cheng
Journal: Journal of Clinical Oncology (2024)

e12615 Background: The KEYNOTE-522 trial showed a significant improvement in pathological complete response (pCR) and event-free survival (EFS), leading to the FDA approval of pembrolizumab (pembro) combined with NACT for high-risk, early-stage TNBC. However, it utilized q3-week dosing for doxorubicin + cyclophosphamide (AC), not the ddAC regimen, which showed superior overall survival (OS) in the CALGB 9741 and EBCTCG trials. Consequently, the superiority of the KEYNOTE-522 regimen over ddAC remains uncertain. This retrospective case-control study compares TNBC patients treated with the KEYNOTE-522 regimen to controls treated with ddAC-NACT, reporting real-world efficacy and safety. Methods: Early-stage TNBC patients treated at our institute from Jan 2019 to Dec 2022 were included. Descriptive statistics outlined patient characteristics and clinicopathological data. Relative risk (RR) for pCR was calculated with a 95% confidence interval, and Kaplan-Meier estimated 1-year EFS and OS. Results: 97 patients were included, with 40 receiving pembro-NACT. Patient demographics and clinicopathological features didn't differ significantly, except for race (p = 0.047). Dose interruption was more common in the pembro group (p &lt; 0.0001); nevertheless, most patients in both arms completed NACT and underwent surgery, mainly mastectomy. Immune-related adverse events reflected current reports. The pembro arm had a 1.43 times higher likelihood of pCR, but it didn't reach significance (RR=1.43, 95% CI: 0.89-2.28). Univariable associations between pCR and age, race, dose interruption, and dose of dexamethasone were not statistically significant; a multivariable model was not fitted for this reason. 1-year EFS and OS were not statistically different between the treatment arms (Table 1). Conclusions: In this real-world analysis, we observed a trend toward a higher rate of pCR in the KEYNOTE-522 compared to the ddAC regimen. Despite more dose interruptions with pembro, the 1-year EFS and OS were not significantly affected. While the more recent 5-year results from the KEYNOTE-522 trial have validated enhanced EFS, with OS data yet to mature, our findings didn't reveal clear short-term benefits. Larger studies are needed to assess long-term benefits, specifically in comparison to previously established standard therapies. [Table: see text]
Impact of the integration of remote clinical oncology pharmacists into routine precision medicine workflows on biomarker testing rates within The US Oncology Network community-based practices.
Authors: Natalie Greisl, Brittney Hale, Melissa Carroll, Judy Cho, Hilary Conkling, Caroline Farag, Juna Jovani, Meredith Keisler, Daniel Kendzierski, Andrea Roman, Josh Howell, Shannon Hough, Beth Koselke
Journal: Journal of Clinical Oncology (2024)

e13813 Background: The US Oncology Network implemented a centralized, remote clinical oncology pharmacist review program (ClinReview) into select community-based practices. Initially, pharmacists were integrated into a precision medicine workflow process to increase biomarker testing rates among patients receiving adjuvant treatment for non-small cell lung cancer, with recommendations achieving a 100% acceptance rate. Following this success, metastatic prostate cancer patients were incorporated into the established workflow, following updated guideline recommendations for both germline and somatic testing and the 2023 approvals of PARP inhibitors in the first-line treatment setting. With previously reported testing rates only reaching 60%, we sought to evaluate the impact of the pharmacist integration into the precision medicine workflow on biomarker testing in metastatic prostate patients. Methods: Over a 4-month period, ClinReview remotely identified patients with metastatic prostate cancer during normal order review. The EMR was reviewed to assess germline and somatic testing status. If testing was not ordered, the pharmacist sent a recommendation to the treating provider. Initial testing rates for germline and somatic testing, BRCA+ status and provider acceptance rates for testing recommendations were collected. Additional data was collected utilizing a de-identified database. While additional data collection is ongoing, descriptive statistics were utilized to analyze data and the impact of the pharmacists’ interventions. Results: Across 9 practices, 142 patients were initiated on treatment for metastatic prostate cancer. At the time of initial assessment, germline and somatic testing was not ordered in 50% and 37% of patients, respectively. Pharmacists recommended additional testing in 61 patients (43%) with a 73% provider acceptance rate. Findings showed equitable testing rates across racial demographics. Pharmacist workflow integration enhanced combined germline and somatic testing rates, demonstrating an improvement from a baseline of 57% up to 77% currently. Conclusions: Community oncology practices seek to provide high-value care, including offering the most current evidence-based precision medicine testing. These findings highlight the continued need for improved somatic and germline testing in metastatic prostate cancer. However, the implemented precision medicine pharmacist workflow demonstrates the positive impact a clinical pharmacist can have on both testing rates and the potential to improve therapeutic offerings within this growing treatment space. [Table: see text]
Transcriptional mechanisms of phenotypic plasticity in glioblastoma.
Authors: Ishita Mukherjee, James H. Park, Anoop P. Patel, Nitin S. Baliga
Journal: Journal of Clinical Oncology (2024)

e14027 Background: Primary glioblastoma (GBM) tumor cells exhibit plasticity and can adopt different cellular states that exhibit dynamic transitions between states. This could be one of the mechanisms for treatment escape and leads to poor prognosis in GBM. In this regard, we sought to uncover transcriptional regulatory mechanisms responsible for this phenotypic plasticity in GBM. Methods: Standard of care (SOC) treatment (radiation and temozolomide) modulates transcriptional regulatory networks (TRNs) of the tumor cells and drives treatment resistance. Since TRNs could be key mechanistic drivers for state transitions, integrated single-cell RNA sequencing (scRNAseq) data of primary and relapse patient samples (11) were analyzed with scMINER. Our method uses a systems biology framework to identify cell states (St_1 to St_n) in terms of regulatory networks and their activities. Clustering of co-regulated gene modules (regulons), enabled the identification of transcriptional programs and regulatory mechanisms that specify tumor cell states. Results: Activity patterns of 38 transcriptional programs clustered tumor cells from the patients into 21 states. Preliminarily, we observed common regulatory network cell states (St_1, St_2, St_5, St_6) across patient tumors. Additionally, primary tumor cells of a patient (UW14) transitioned from initial cell state(s) observed across multiple patients (e.g., St_1) to a recurrent state (e.g., St_9) through a trajectory driven by transcription factors (TFs). Herein, scMINER regulatory network inference method also defines master TFs (TFs that regulate the majority of the other TFs in the network) that were used to characterize initial (St_1) or recurrent (St_9) cell states. Moreover, certain transcription factors (22) and their co-expressed target genes (regulons) also exhibit variation in expression across the pseudotime trajectory (from St_1 to St_9) including masterTFs such as SOX9 and MECOM. Conclusions: Therefore, we observed that shared cell states may exist across patients (primary and relapse) although in different proportions. Our analysis suggests a de-differentiation trajectory from neuronal cells to developing GBM stem cells and predicts transcription factors that could be playing an important role therein. Moreover, similar transcriptional regulatory mechanisms may promote transitions between primary and recurrent tumor cell states that exhibit phenotypic plasticity.
Establishing a protocol to increase racial/ethnic minority enrollment on an active radiation oncology randomized clinical trial.
Authors: Ulysses Grant Gardner, Otis W. Brawley, Elizabeth E Obi, Kristin Janson Redmond, Shearwood McClelland
Journal: Journal of Clinical Oncology (2024)

TPS1638 Background: In the United States (US), underrepresented racial/ethnic groups lack ample enrollment in clinical trials, yielding ungeneralizable trial results. Barriers to increasing minority enrollment include decreased awareness of clinical trials, lack of access, financial burden and toxicity, medical system mistrust, and discordant physician-patient demographics. The ongoing Spine Patient Optimal Radiosurgery Treatment for Symptomatic Metastatic Neoplasms (SPORTSMEN) clinical trial (NCT05617716) has a study design to actively accrue minority patients. We present our protocol addressing key targets to increase minority enrollment on this randomized, phase II clinical trial. Methods: Adults with evidence of symptomatic spine metastases are eligible. Baseline demographics (including race/ethnicity) are reported for statistical analysis. Our protocol seeks to minimize barriers to minority enrollment and targets four key areas. Access to care: SPORTSMEN involves institutions located in zip codes with diverse ethnic populations, presently located in regions 46% and 70% African American. Clinical trial design: SPORTSMEN has a prespecified goal of accruing patients to mirror US census representation. The rate of minority enrollment will be reviewed periodically at the discretion of the Data Safety and Monitoring Board. Community outreach and engagement: The trial team will engage with local health care systems to create an alliance within different oncology specialties to provide the basis and benefit for SPORTSMEN and patient-centered education on eligibility criteria, rationale, and intended outcomes. Our principal focus will be providers in prostate, breast, and lung cancers as minorities with these primary site malignancies have a higher propensity to be trial-eligible. Furthermore, we understand the historical mistrust of minorities for the medical community. Therefore, we will engage local grassroot organizations such as churches, community outreach centers, and social clubs to increase awareness of clinical trials and to help foster trust. Financial burden and toxicity: SPORTSMEN does not have direct enrollment costs. A short-course treatment regimen is used to minimize the number of treatment visits required allowing for decreased resources for travel, time lost at work, and additional childcare or eldercare needs. Financial toxicity will be objectively quantified using the validated COST-Functional Assessment of Chronic Illness Therapy survey. Increasing clinical trial diversity is a challenge that must be addressed with meaningful intent to present robust Level 1 data that broadens the understanding of treatment response in all demographics. Our protocol takes a patient-centered approach to achieve the objective of concordant racial/ethnic representation in a randomized clinical trial. Clinical trial information: NCT05617716 .
A new model to enhance enrollment of diverse participants to therapeutic clinical trials.
Authors: Patricia Y. Ryan, Julia M. Brain, Sara I. Pai, H. Kim Lyerly, Jennifer Lynn Harris
Journal: Journal of Clinical Oncology (2024)

TPS1640 Background: Disparities in United States clinical trial participation are well described, with the inclusion of only 8% Black, 6% Asian, and 1% Hispanic participants in phase III oncology trials supporting US FDA filings in 2020. The FDA, Cancer Moonshot, and ASCO-ACCC have issued guidance, sponsored initiatives, and developed strategies to raise awareness around the importance of equality, diversity, and inclusion at centers with current clinical research capabilities. Centers with ongoing research capability are typically large academic or private practice sites located in urban areas. There is an urgent need to expand clinical trial offerings to rural communities as geographic constraints disproportionally limit people of color and people of low socioeconomic status from accessing innovative drugs offered only through clinical trials. An additional contributing factor to low enrollment of diverse participants is a lack of racial, ethnic, gender, and geographic diversity amongst clinical trial investigators, who may be more relatable and, thus, effective at recruiting underrepresented patients to clinical trials. Lastly, to provide high quality care for their patients, clinical investigators must have ability to identify and select trials which address the specific needs of the patients within their practice. We hypothesize that a tool which improves identification and inclusion of an expanded investigator pool will result in improved diversity of clinical trial participation. Methods: We have developed a bi-directional matching software program that allows healthcare providers to define their areas of interest and match them to available pharmaceutical company clinical trial opportunities. The software, Golgi-CONNECT, will be piloted with up to 500 oncology-focused healthcare providers across a diverse geographic landscape and up to 6 pharmaceutical companies of varying sizes to evaluate the functionality and usability of the application. Additionally, HCP-reported barriers to clinical trial conduct, inclusive of financial, infrastructure, training, mentoring and lack of support staff will be collected.
A paradox of size: Case-volume, financial outcomes, and risk in the enhancing oncology model baseline period.
Authors: Puneeth Indurlal, Hope Ives Thomas, Jason Altieri, Jody S. Garey, Jessica Neeb, Stuart George Staggs, Lalan S. Wilfong
Journal: Journal of Clinical Oncology (2024)

e13809 Background: The Centers for Medicare and Medicaid Innovation’s (CMMI) Enhancing Oncology Model (EOM) is a risk-bearing, population-based value-based care (VBC) model requiring participating physician group practices (PGP) to take financial risk and performance accountability for episodes of care for seven common cancers. We studied the association between case volume, financial outcomes, and risk in the EOM. Methods: Using deidentified public use EOM baseline episode files (2016 - 2020), and the EOM Price Prediction Model provided by CMMI, we calculated the predicted baseline price (BP) per episode and savings (difference between baseline price and actual expenditures (AE)), grouped PGPs per baseline period by episode count (case volume), and evaluated the risk (variation of savings). ANOVA, F-test, and pair-wise tests were used to evaluate statistical significance. Results: Two-thirds of the 16,348 PGP appearances per time-period (n) had &lt;72 episodes (average: 93.8, median: 36). Table 1 shows population and savings metrics. There was a significant effect of episode counts on savings (ANOVA/F-test: F(5,16342) = 24.5, p&lt;0.0005). Post hoc pair-wise t-tests (Holm correction to adjust p) indicated groups with &lt;72 episodes had increased risk (4.5:1, p&lt;0.0005) and &gt;361 episodes had the least risk (p&lt;0.0005). Groups with &lt;72 episodes had four times the median savings than groups with &gt;361 episodes. Conclusions: As expected with the law of large numbers, groups with fewer episodes are exposed to higher risk and extremes of financial outcomes in EOM-like models while paradoxically generating better savings. The impact of case-mix differences among groups is apt for further exploration. Differences in PGP dynamics and provider like-mindedness with care transformation is one possible explanation for this paradox. Future models should incorporate risk mitigating modeling techniques (case-volume adjustments) or facilitate easier partnering arrangements to engage groups with fewer episodes. [Table: see text]
Time to treatment and follicular thyroid cancer survival: A SEER database analysis.
Authors: Laura Cogua, Connor Tupper, Peter T. Silberstein
Journal: Journal of Clinical Oncology (2024)

e13794 Background: Follicular thyroid cancer (FTC) is a prevalent endocrine malignancy, typically managed with surgical resection. Few studies have investigated the optimal time of surgery for FTC at a national registry level. The aim of this study is to examine the impact of delaying surgical intervention on survival in FTC. Methods: Patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with FTC between 2000-2020 were selected. Additional variables were collected including age, sex, race, stage, surgical status, radiation status, time to treatment, household income, and population size. Kaplan-Meier, and one- and five-year logistic regression analyses were performed. Results: A total of 10,478 patients were included of which 95.5% underwent surgical management. There was a 98.3% and 96.4% survival rate at one- and five-years, respectively. On Kaplan-Meier, those who underwent surgery survived longer (p&lt;0.001). Additionally, patients treated within one month of diagnosis survived significantly better than those treated later (p&lt;0.001). On one-year logistic regression, higher staging was associated with worse survival while those who received surgery, radiation, and lived in counties with a median household income &gt;$75,000 had better survival (p’s&lt;0.05). On five-year logistic regression, patients older than 50 years old and higher staging were associated with worse survival while those who received surgery had better survival (p’s&lt;0.001). No differences were observed for time to treatment at one or five years. Conclusions: Our results show that surgical management is associated with improved survival in patients with FTC. On univariate analysis, a duration of one month or less between diagnosis and treatment was associated with improved survival. However, on multivariate analysis, only surgical management, radiation, and median household income &gt;$75,000 were associated with improved survival.