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Participation of women and early-career faculty in hematology and medical oncology board review lecture series has not been studied previously. We aimed to evaluate gender and early-career faculty disparities in hematology and medical oncology board review lecture series. Speakers at major hematology and/or oncology board review lecture series meetings in the United States were analyzed in this cross-sectional study during a 5-year period from the years 2017 through 2021. Data about the lecture topic, field, speaker’s gender, years of experience, and the frequency at which the lecture was given by the speaker were collected. Of 386 speakers participating, 315 (81.6%) were ABIM (American Board of Internal Medicine)-certified. A total of 1,224 board review lectures were given in the studied period, of which 1,016 (83%) were given by an ABIM-certified speaker. Women constituted 37.7% of all speakers, with less than 50% representation in five out of six courses. Lectures discussing malignant hematology topics had the lowest proportion of women presenters (24.8%), followed by solid tumors (38.9%) and benign hematology lectures (44.1%). Faculty with more than 15 years since initial certification presented more than 50% of lectures. The median time from initial hematology or medical oncology certification to lecture presentation was 12.5 years and 14 years, respectively. A positive trend in the participation of women was found at all board review conferences across the studied period. Our data suggest that women and early-career faculty participation in hematology and oncology board review series is inadequate.

IntroductionAmplification of 3q is the most common genetic alteration identified in squamous cell carcinoma of the lung (LUSC) with the most frequent amplified region being 3q26-3q28.MethodsIn this analysis, we aim to describe the prognostic relevance of 3q by focusing on a minimal common region (MCR) of amplification within 3q constituted by 25 genes. We analyzed 511 cases of LUSC from The Cancer Genome Atlas (TCGA) and included 476 in the final analysis.ResultsWe identified a 25-gene MCR that was amplified in 221 (44.3%) cases and was associated with better disease specific-survival (DSS) (NR versus 9.25 years; 95% CI [5.24-NR]; log-rank p=0.011) and a progression-free interval (PFI) of 8 years (95% CI [5.1-NR]) versus 4.9 years (95% [3.5-NR]) (Log-rank p=0.020). Multivariable analysis revealed MCR amplification was associated with improved DSS and PFI.ConclusionAmplification of the 25-gene MCR within 3q was present in 44% of this cohort mainly composed of Caucasian patients with early-stage LUSC. This analysis is a strong indicator of the prognostic relevance of the 25-gene MCR within 3q. We are further evaluating its prognostic relevance in a racially diverse patient population with advanced LUSC.

Background: The use of staplers in surgical repair of the pharynx after laryngectomy has gained traction in recent years, with differing results. Objective: In this study, we compare the use of stapler suturing (SS) after laryngectomy in comparison with the manual suturing (MS) technique in laryngeal cancer patients regarding pharyngocutaneous fistula (PCF) formation, operative time, blood loss, margin status, and length of hospital stay. Methods: We conducted a retrospective cohort study of laryngeal cancer patients undergoing pharyngeal repair after total laryngectomy by either a stapler or manual suturing. Demographic data, stage of disease, postoperative complications, duration of hospital stay, and operative time were collected. Results: A total of 59 laryngeal cancer patients were included, of which 22 underwent SS and 37 had MS. Our cohort was predominantly males (98%), and similar mean ages were observed across both suturing groups (60.5 vs 59.9, P = 0.83). Negative margins were more frequent with SS (100% vs 86.5%, P = 0.13) yet this difference was not statistically significant, whereas preoperative tracheostomy procedure was present more in MS patients (43.2% vs 0, P = 0.003). Lymph node involvement was higher in the manual suturing cohort, yet this difference was statistically insignificant (41.2% vs 25%, P = 0.49). The muscle flap procedure was significantly higher in the MS cohort (70.3% vs 20%, P = 0.001). In both groups, comparable PCF rates were noted (13.3% vs 10.8%) and there was no association between salvage laryngectomy and PCF occurrence in the entire cohort. For surgery details, there was no statistical difference between both groups in blood loss, hospitalization length, or oral feeding start. Only surgical time was significantly lower in the stapler cohort (277 vs 372.6 minutes, P = 0.000). Conclusion: Both suturing techniques did not show any statistically significant difference in PCF rates. However, was markedly reduced with stapler use in comparison to manual suturing. Further randomized studies with larger sample size are needed to validate the role of stapler suturing for pharyngeal repair.

The gut microbiome refers to microorganisms and their genetic material influencing local and systemic inflammation. Inflammation is known to contribute to cancer development, progression, and treatment. Evidence suggests that modulating the gut microbiome may affect responses to various cancer therapies. The gut microbiota has been suggested to have an impact on immunotherapy efficacy, especially the currently widely used immune checkpoint inhibitors in various malignancies. Microbial interventions like fecal microbiota transplantation, various probiotics, or even antibiotics can increase or decrease the tumor’s sensitivity to immunotherapy. However, not all tumors react in the same manner, highlighting the tumor microenvironment heterogeneity across tumor types and the influence this has on the crosstalk between the microbiome and therapy outcomes. In this study, we intend to review the association between the gut microbiota and immunotherapy response in cancer patients and the factors regulating this interaction.

Introduction: Triple-negative breast cancer (TNBC) is an aggressive type that lacks targeted therapies posing a challenge in its management. This necessitates identifying novel targets that may play a role in the regulation and progression of TNBC. There is renewed interest in targeting the androgen receptor (AR) since it is expressed in TNBC and plays an important role in its biology. Studies have shown that AR can influence the behavior of TNBC via affecting the of expression microRNA molecules (miRNAs), which can modulate the expression of cancer-regulatory proteins. We aimed to profile the expression of miRNAs in human TNBC tissue samples in relation to the expression of AR and investigate their prognostic value. Methods: The expression of 84 miRNAs in 24 TNBC tissue samples (12 AR-positive and 12 AR-negative) was examined using PCR array technology. Several bioinformatics tools were then utilized on the differentially expressed miRNAs (DE-miRNA) to determine the potentially affected protein targets and signaling pathways. Potential target genes (DEGs) for each miRNA were identified by miRWalk2.0. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were conducted for the target genes using the DAVID 6.8 bioinformatics tool. String and Cytoscape were used for establishing a PPI network and identifying the hub genes. Jamovi2.2 was used for the statistical analysis. Results: A total of 7 DE-miRNAs were found to be significantly expressed in the tissue samples relative to AR expression. Good and poor survival outcomes, respectively, were found to be linked to miR-328-3p and miR-489-3p. Interestingly, these two miRNAs were found to be up-regulated in AR-positive tumors. The association of miR-328-3p with AR corroborates our previous findings that this miRNA is up-regulated upon AR activation in TNBC cells. Two other miRNAs, miR-17-5p and iR-193b-3p, were found to be significantly associated with high T3 and low N2 status, respectively. Gene Ontology (GO) analysis for the 7 DE-miRNAs indicated a role in the regulation of the cell cycle in various cellular components (CC) such as the “nucleus”, “centrosome”, and “transcription factor complex”. GO analysis also showed enrichment in kinase and transcription factor activities. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses retrieved numerous relevant signaling pathways such as that of the TGF-beta, MAPK, Th17 cell differentiation, and endocrine resistance. Conclusion: This study offers an understanding of the molecular etiology of TNBC and further implicates miRNAs in mediating the effect of AR on TNBC. We also provide an integrative analysis of the AR-miRNA-TNBC gene network that can help in identifying potential therapeutic targets. Keywords: Breast Cancer, TNBC, Bioinformatics, miRNA, Androgen Receptor Citation Format: Bayan O. Abu Alragheb, Hassan Abushukair, Maysa Al-Husseini, Randa Bawadi, Mamoun Ahram. The association of androgen receptor with microRNA expression in triple-negative breast cancer. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3772.

Bruton tyrosine kinase inhibitors (BTKi) are important treatment options in Waldenström's macroglobulinemia (WM). Whether second-generation BTKi are associated with improved outcomes and/or better safety profile remains unclear. We did a systematic review and meta-analysis of clinical trials that reported data on the outcomes of patients with WM who received either first- or second-generation BTKi in the period between January 2010 and August 2021. Studies with twenty or fewer patients were excluded. The primary outcomes were efficacy measured by response and survival data. Eleven studies met the eligibility criteria and were included in the final analysis (n = 730 patients). A total of 298 patients received 1st-generation BTKi and 432 received a 2nd-generation BTKi. Pooled overall response rate (ORR) and major response rate (MRR) for both generations were similar (94.2% and 78.5% in 1st vs. 88.9% and 75.1% in 2nd, respectively). MRR for both generations was higher in MYD88 Mut/CXCR4 WT patients compared to MYD88 Mut/CXCR4 Mut patients (odds ratio [OR]: 3.9, 95% CI: 2.2 to 5.5). Pooled 18-mo progression-free survival (PFS) was similar for both generations (88.5% vs. 87.3%). Grade 3/4 atrial fibrillation was higher in 1st-generation BTKi (3.1% vs. 0.4%); however, grade-3/-4 infections and neutropenia were more frequent in 2nd-generarion BTKi (20.9% vs. 13.2%, 17.7% vs. 12%, respectively). The efficacy of 1st- and 2nd-generation BTKis is comparable. The 1st-generation BTKi were associated with a higher risk of atrial fibrillation, whereas infections and neutropenia occurred more frequently in 2nd-generation BTKi.

Deep brain stimulation (DBS) has been introduced as a treatment option for multiple sclerosis (MS) related tremor. Recent emerging studies have investigated its efficacy and safety, yet no study has systematically assessed the evidence on this topic. Zali and colleagues have conducted the first systematic review and meta-analysis on the use of DBS in MS tremor patients. In this letter, we highlight some points in their meta-analysis regarding high heterogeneity levels that reflect some methodological concerns related to pooling studies with considerable variability. We also suggest some approaches to address this problem.

Extended resection for non-small cell lung cancer (NSCLC) with T4 left atrium involvement is controversial. We performed a systematic review and meta-analysis to evaluate the short- and long-term outcomes of this treatment strategy.We searched the PubMed database for studies on atrial resection in NSCLC patients. The primary investigated outcome was the effectiveness of the surgery represented by survival data and the secondary outcomes were postoperative morbidity, mortality, and recurrence.Our search identified 18 eligible studies including a total of 483 patients. Eleven studies reported median overall survival and 17 studies reported overall survival rates. The estimated pooled 1, 3, 5-year overall survival rates were 69.1% (95% CI 61.7-76.0%), 21.5% (95% CI 12.3-32.3%), and 19.9% (95% CI 13.9-26.6%), respectively. The median overall survival was 24 months (95% CI 17.7-27 months). Most studies reported significant associations between better survival and N0/1 status, complete resection status, and neoadjuvant therapy.Extended lung resection, including the left atrium, for NSCLC is feasible with acceptable morbidity and mortality when complete resection is achieved. Lymph node N0/1 status coupled with the use of neoadjuvant therapies is associated with better outcomes.