tbuckley/cabot-search huggingface dataset:
The impact of an inclusion council in an independent community oncology practice.
Authors: Mark T. Fleming, Kristina Lyons, Roshonda Poole, Margot Richards, Sonia Hepburn, Tahj Ali-Spencer, Tifany Lewis
Journal: Journal of Clinical Oncology (2024)

e21018 Background: Mainly present in academic hospital centers, Diversity Equity, and Inclusion (DEI) efforts have been largely left out of private practice. We previously reported on the impact of DEI training at VOA after our initial launch of the Inclusion Council in August 2020. VOA’s Inclusion Council continues its mission to further advancements in promoting a safe inclusive environment in the private practice setting. Methods: The methodology employed involved the administration of an anonymous comprehensive nine-question survey by the VOA Inclusion Council to assess the effectiveness of its ongoing efforts since its inaugural launch in 2020. The survey was meticulously crafted to capture the nuanced insights from employees regarding their knowledge and perceptions of the Inclusion Council’s impact on workplace dynamics. The questions were designed to gauge the extent to which the Council has successfully fostered an inclusive environment, promoted diversity, and identified any potential challenges faced by employees. The survey was distributed to all employees, ensuring a diverse range of perspectives was considered. This methodological approach aimed to provide a robust understanding of the council’s effectiveness through the direct input of those within the organization, thereby contributing valuable data for the evaluation of its initiatives. Results: Summary of employee respondent’s views on Inclusion Council helping foster a culture of inclusion in the workplace. A total of 147 employees responded. 68% of respondents agreed or strongly agreed that the Inclusion Council helped foster a culture of inclusion in the workplace. Conclusions: An Inclusion Council, focused on DEI efforts, can help foster a culture of inclusion in the workplace. Veteran and new employees agreed the Inclusion Council has helped foster a culture of inclusion in our community oncology practice. [Table: see text]
A comparison of real-world incidence of <i>EGFR</i> exon 20 insertion mutations among patients with NSCLC in five Asian markets, stratified by testing methodology.
Authors: Pieter De Richter, Mei Yee Koo
Journal: Journal of Clinical Oncology (2024)

e20622 Background: Despite the arrival of drugs targeting EGFR exon 20 insertions mutations (ex20ins) in non-small cell lung cancer (NSCLC), testing practices for this specific mutation vary widely between hospitals. In addition, there is a lack of real world data on incidence of ex20ins in different countries in Asia. This study tracks real-world ex20ins incidence by country/region as well as by methodology across 5 different Asian markets. Methods: Ipsos’ Exon 20 Insertion Tracker is an ongoing physician-reported syndicated study. Hospitals in Asia (n = 7 in South Korea; n = 5 in Taiwan; n = 4 in India; n = 5 in Thailand; n = 1 in Hong Kong) were asked to submit data on total number of NSCLC patients tested for EGFR mutations using single marker tests vs multi-gene panel tests, and subsequently asked how many tested positive for ex20ins. Data were collected online on a regular basis from September 2022 in South Korea and Taiwan, from January 2023 in India, and from September 2023 in Thailand and Hong Kong, until December 2023 in all markets. A total of n = 7,657 EGFR-tested patients in South Korea, n = 2,260 in Taiwan, n = 3,970 in India, n = 407 in Thailand and n = 114 in Hong Kong were reported on. Results: Incidence of ex20ins was markedly higher in Hong Kong (3.5%) and Taiwan (3.7%) than in South Korea (1.6%), India (1.4%) and Thailand (1.0%), pointing to a potentially higher incidence in Greater China compared to other parts of Asia. Among this cohort, the use of panel testing for EGFR mutations was highest in India (99%) and lowest in Taiwan (1%). Across the markets, incidence of ex20ins appears to be somewhat higher among those tested with single-marker EGFR tests (2.2%) than those tested with panel-based tests (1.4%), although the opposite was observed in Thailand and Hong Kong. Conclusions: In this large study based on testing results from over 14,400 EGFR-tested patients across 5 different markets in Asia, clear differences in observed incidence of ex20ins mutations were observed, with the incidence in Taiwan being nearly 4 times as high as that in Thailand. This highlights that different testing and biomarker sequencing strategies may be necessary in markets with the highest observed incidence. A secondary finding from this study is that test methodology does appear to have an impact on observed incidence, though this is in part due to very different testing approaches (single-marker vs panel-based) between markets, with the majority of hospitals included in the study in Taiwan preferring a single-marker approach. [Table: see text]
Revolutionizing global hematology-oncology education: Assessing the two-year impact of a digital platform on socioeconomic equity and inclusivity against gender disparities.
Authors: Yan Leyfman, William B. Wilkerson, Viviana Cortiana, Jade Gambill, Gayathri P. Menon, Muskan Joshi, Elizabeth Jean Heller, Keira Smith, Helena S. Coloma, Maduri Balasubramanian, Emad B. Zahid, Alexandra Van de Kieft, Harshal Chorya, Rabab H. Abbas, Jenna Fadi Ghazal, Blaise Bowers, Ahmed Azeez, Chandler H. Park
Journal: Journal of Clinical Oncology (2024)

e21000 Background: Social media has transformed the global exchange of knowledge, with 77.4% of cancer patients relying on it as a primary source of information especially in resource-limited areas. Given that a third of social media posts contain misinformation that can have negative ramifications, MedNews Week (MNW) was developed as a digital platform featuring presentations by global authorities to enhance global oncology education through its freely accessible programming. In light of the gender disparity in speakers at scientific symposia, where females represent &lt;30%, MNW strived to combat gender inequity by featuring them in equal proportion to males. The goal of this study was to evaluate the ability of MNW’s virtual oncology education platform to combat socioeconomic (SE) education inequity while promoting gender inclusivity. Methods: From January 2022 to 2024, MNW hosted 36 distinguished global oncology leaders as Keynote Speakers (Mean H-index=50.09). Data on viewership and outreach were collected from MNW's social media accounts. A mixed-method approach was employed to determine audience and speaker demographics, and engagement. Results: MNW achieved a Healthcare Social Score amongst the top 0.07 percentile of global healthcare influencers on Twitter. Over the past year, MNWoncology programming experienced a 10.5-fold increase in mean attendance, reaching 743,991 people in 95 countries globally, with 23 classified as low-to-middle SE status. In 2023, MNW followers exhibited a female predominance (48.8%), mainly from non-healthcare fields (60.0%). MNW showcased gender parity among oncology keynote speakers, with female lecturers drawing similar attendance as males (p=0.89, two-tailed unpaired t-test). Conclusions: MNW has established a growing digital platform, while removing financial barriers to effectively engage lay audiences, particularly in underserved regions. MNW's commitment to empowering female speakers exemplifies its dedication to inclusivity in a historically imbalanced field. This underscores MNW's success in fostering inclusivity, by driving engagement of those traditionally underserved, and positively impacting oncology education globally. [Table: see text]
Efficacy and safety of time-of-day infusion of pemetrexed plus platinum and paclitaxel plus platinum for patients with advanced non-small cell lung cancer: A retrospective study.
Authors: Li-Yue Sun, Quan-An Xu, Xian Xu, Ke-Xin Xian, Xin-Xin Zeng, Hua-Gen Li, Xu-Hui Zhang
Journal: Journal of Clinical Oncology (2024)

e20557 Background: Retrospective studies suggest that administering chemotherapy infusions in the morning can enhance treatment efficacy and mitigate side effects in non-small cell lung cancer (NSCLC) patients. However, the effectiveness of chronotherapy using pemetrexed plus platinum (AP) and paclitaxel plus platinum (TP) in advanced NSCLC chemotherapy remains unexplored. This study aims to evaluate the impact of AP and TP chrono-chemotherapy (CCT) on treatment response and adverse events in advanced NSCLC patients. Methods: We retrospectively analyzed 78 advanced NSCLC patients treated with AP (AP cohort) and 50 advanced NSCLC patients treated with TP (TP cohort) at Guangdong Second Provincial General Hospital from 2018 to 2021. Based on previous research, we classified patients who received chemotherapy infusions more than twice after 2:00 PM as the afternoon (PM) group, while the rest were categorized as the morning (AM) group. Treatment response was evaluated using the Response Evaluation Criteria in Solid Tumors Criteria V.1.1. The primary endpoint was progression-free survival (PFS). All adverse events were identified and graded according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 5.0. Results: In the AP cohort, the AM group exhibited a longer PFS compared to the PM group (AM vs. PM, n = 26 vs. n = 52, 43.0 vs. 13.0 months, p = 0.001). However, no significant difference was observed in PFS in the TP cohort (AM vs. PM, n = 23 vs. n = 27, 11.0 vs. 22.0 months, p = 0.501). Subsequent subgroup analysis in the AP cohort favored the AM group across all major subgroups for PFS treatment effect. In contrast, the TP cohort subgroups showed a PFS benefit only in the smoking patients of the PM group. Furthermore, the analysis of adverse reactions revealed similar incidences of any treatment emergent adverse events (TEAE) in both AP and TP cohorts (AM vs. PM, 92.3% vs. 86.5% in AP cohort and 95.7% vs. 100.0% in TP cohort), and grade 3 TEAEs (AM vs. PM, 34.6% vs. 21.2% in AP cohort and 39.1% vs. 29.63% in TP cohort). The most common adverse events were anemia (73.1%), leukopenia (57.7%), and elevated ALT (46.2%) in AP cohort and anemia (100%), leukopenia (65.2%), and hypoalbuminemia (47.8%) in TP cohort. Univariate and multivariate analyses indicated that afternoon infusion of AP chemotherapy (p = 0.009) was an independent prognostic factor for NSCLC. Conclusions: AP treatment administered in the morning may enhance PFS in advanced NSCLC, while TP remains unaffected. This suggests that CCT could potentially enhance the efficacy of individualized chemotherapy in advanced NSCLC.
5-hydroxymethylcytosine in cell-free DNA as liquid biomarker for immune checkpoint inhibitor therapy in non–small cell lung cancer.
Authors: Zainub Ajmal, Jianming Shao, Randall Olsen, Saro Kasparian, Chuan He, Eric Bernicker, Zejuan Li, Jun Zhang
Journal: Journal of Clinical Oncology (2024)

e20563 Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1 (PD-1), and its ligand (PD-L1) are the mainstay of treatment for metastatic non-small cell lung cancer (NSCLC) in patients lacking targetable driver mutations. However, optimal predictive biomarkers are lacking. We used a plasma cell-free DNA (cfDNA) 5-hydroxymethylcytosine (5hmC) signature-based predictive model to assess treatment response and potentially select patients eligible for ICI monotherapy. Methods: 40 plasma samples were collected from adult patients with stage III or IV lung cancer at Houston Methodist Hospital between 2019 and 2022. These were divided into a training (n = 24) and validation (n = 16) set. By identifying genes associated with progression free survival (PFS), a 16-gene signature was used to develop a 5hmC predictive model. A weighted predictive score (wp-score) based on the model was calculated for each patient and grouped into low and high wp-scores. Results: Low wp-scores were associated with higher objective response rate(ORR) in both training and validation set and better correlated with response rates compared to PD-L1. In the training set, PFS was longer in low wp-scores compared to high wp-scores (median 12.3 versus 3.0 months; p = 3.5x10 -6 ; hazard ratio (HR) 4.6x10 -10 ). This was also seen in the validation set (median 7.6 versus 1.8 months p = .0012; HR 0.12). Contrarily, high ( &gt; 1%) or low ( &lt; 1%) PD-L1 was not associated with PFS (median 6.8 versus 6.0 months; p = .40; HR 0.70; 95% CI, 0.30–1.60) or overall survival (OS) (median 10.1 versus 12.0 months; p = .38; HR 0.56; 95% CI, 0.15–2.10). 15 out of the 40 total patients received ICI monotherapy. Among these, low wp-scores (n = 8) were significantly associated with longer PFS compared to high wp-scores (n = 7), (median 19.6 versus 2.8 months; p = .00073; HR: 0.059). OS although longer, was not significant among the two groups (median 38.1 versus 10.5 months; p = .12). Conclusions: Our study provides a proof of concept that cfDNA 5hmC signature can be used to predict response to ICI therapy and select patients appropriate for monotherapy. It is a more sensitive and specific biomarker to PD-L1. Larger studies are underway to further validate cfDNA 5hmC based-signature predictive model. [Table: see text]
Efficacy and safety of triplet nivolumab, relatlimab, and ipilimumab (NIVO + RELA + IPI) in advanced melanoma: Results from RELATIVITY-048.
Authors: Paolo Antonio Ascierto, Reinhard Dummer, Caroline Gaudy-Marqueste, Samantha Bowyer, Evan J. Lipson, Eleonora Ghisoni, Mark R. Middleton, Barbara Ratto, William Joseph Jackson, Alicia Cheong, Sourav Mukherjee, Jenny Wu, Georgina V. Long
Journal: Journal of Clinical Oncology (2024)

9504 Background: NIVO (anti–PD-1 antibody) is approved as monotherapy and in combination with either RELA (anti–LAG-3 antibody) or IPI (anti–CTLA-4 antibody) for the treatment of patients (pts) with advanced melanoma. RELATIVITY-048 (NCT03459222) is a phase 1/2, nonrandomized trial evaluating immuno-oncology (I-O) triplets, including NIVO + RELA + IPI, for pts with select solid tumors. This analysis from RELATIVITY-048 focused on NIVO + RELA + IPI use in the advanced melanoma cohort and is the first disclosure from the study. Methods: Pts with advanced melanoma were treated with first-line NIVO 480 mg Q4W + RELA 160 mg Q4W + IPI 1 mg/kg Q8W until progression or unacceptable toxicity. Prior neoadjuvant/adjuvant therapy, including I-O agents, was permitted if completed &gt; 6 mo before enrollment. Pts with controlled brain metastases were allowed to enroll. Primary endpoints were safety and confirmed objective response rate (ORR), disease control rate (DCR), and median duration of response (DOR) per investigator. The secondary endpoint was progression-free survival (PFS) per investigator (median and 6-mo/12-mo rates). Exploratory endpoints included overall survival (OS; median and 12-mo/24-mo rates). Results: In total, 46 pts were treated. Median follow-up was 49.4 mo (range, 0.4–55.0; database lock, Nov. 1, 2023). Median age was 61.0 y, 8.7% had cutaneous acral melanoma, 50.0% were BRAF positive, 73.9% were LAG-3 positive (≥ 1%), 26.1% were tumor cell PD-L1 positive (≥ 1%), and 6.5% had received prior adjuvant therapy. Median duration of treatment was 5.0 mo (range, 0.0–49.0). NIVO + RELA + IPI had a confirmed ORR of 58.7% and a 48-mo OS rate of 71.7% (table). Any-grade and grade 3/4 treatment-related adverse events (TRAEs) occurred in 44 pts (95.7%) and 18 pts (39.1%), respectively. Any-grade TRAEs led to treatment discontinuation in 19 pts (41.3%). Deaths due to TRAEs occurred in 2 pts (4.3%; rectal hemorrhage and dyspnea [n = 1], immune-mediated myositis [n = 1]). Conclusions: In RELATIVITY-048, NIVO + RELA + IPI demonstrated encouraging efficacy, with a confirmed ORR of 58.7% and a 48-mo OS rate of 69.1%. There were no new safety signals with NIVO + RELA + IPI, and the safety profile was generally consistent with I-O combinations. Given the small sample size, additional studies are needed to confirm the efficacy and safety of NIVO + RELA + IPI. Clinical trial information: NCT03459222 . [Table: see text]
FDG-PET associations with pathological response and survival with neoadjuvant immunotherapy for melanoma.
Authors: Li Zhou, Edward Hsiao, Serigne N Lo, Matteo S. Carlino, George Au-Yeung, Maria Gonzalez, Andrew John Spillane, Thomas Pennington, Julie R. Howle, Kerwin Frank Shannon, Rony Kapoor, Jonathan Stretch, David E. Gyorki, Robyn P.M. Saw, Sydney Ch'ng, Richard A Scolyer, Georgina V. Long, Alexander M. Menzies
Journal: Journal of Clinical Oncology (2024)

9523 Background: This study sought to describe the changes seen with FDG-PET following neoadjuvant immunotherapy in melanoma patients (pts), and explore associations with pathological response and recurrence-free survival (RFS). Methods: Two prospective clinical trial cohorts of stage III pts with RECIST measurable nodal melanoma were included; 1) NeoTrio, 13 pts received 2 doses of preoperative pembrolizumab alone, and 2) NeoPele, 20 pts received 2 doses of pembrolizumab and 5 weeks of lenvatinib preoperatively. All pts underwent baseline and week 6 (preoperative) FDG-PET assessments and all had surgery. PET responses were evaluated based on the modified EORTC criteria. In addition to the standard categories Complete Metabolic Response (CMR), Partial Metabolic Response (PMR), Stable Metabolic Disease (SMD), and Progressive Metabolic Disease (PMD), a novel category was established, near-CMR, where the maximum standardized uptake value (SUVmax) decreased by more than 90%. PET responses were determined while blinded to the outcome data. Pathological response was determined as per INMC criteria. Results: 33 pts were included, 67% male, median age 65 years, 48% BRAF mutant. Pathological response, PET response and correlations are shown in the Table. All 8 (24%) pts achieving CMR or near-CMR obtained major pathologic response (MPR), while the 14 pts (42%) with PMR had variable pathological outcomes (57% MPR, 21% pPR, 21% pNR). For the 6 pts with PMD, 5 (83%) had pNR and the one pts who achieved pCR recurred with brain metastases. After a median 29.9 mo follow-up (95% CI 27.0-33.1), PET response associated with RFS; those with CMR/near CMR had 100% 24mo RFS (nil recurrences to date) while those with PMR or SMD had inferior survival (79% and 80% 24mo RFS), and those with PMD the worst outcomes (17% 24mo RFS, all pts except one have recurred) (p=0.0029). The predictive value of PET and pathology for RFS was assessed using the Cox Proportional Hazards model. 12- and 24-month RFS AUCs of PET and pathology response were similar at 81.5% (95% CI: 67.7-95.3) vs. 80.9% (95% CI: 67.8-93.9), and 83.3% (95% CI: 69.1-97.5%) vs. 80.8% (95% CI: 66.6-94.9), respectively. Conclusions: FDG-PET demonstrates utility in predicting pathological response and survival with neoadjuvant immunotherapy in melanoma. PET may identify pts who are not going to be pathological responders and who have the worst survival outcomes, enabling a potential switch of neoadjuvant systemic therapy. [Table: see text]
Analysis of thromboembolic events in patients with non-small cell lung cancer treated with immune checkpoint inhibitors: A single-center real-world study.
Authors: Tae-Hwan Kim, Cheongin Yang, Yong Won Choi, Minsuk Kwon, Hyun Woo Lee, Seok Yun Kang, Mi Sun Ahn, Jin-Hyuk Choi
Journal: Journal of Clinical Oncology (2024)

e20580 Background: Thromboembolic events (TEEs) are serious complications leading to significant morbidities and mortality in cancer patients (pts). Although incidences of 7-17% for TEEs were reported in non-small cell lung cancer (NSCLC) pts undergoing palliative chemotherapy, there were few reports on TEEs in NSCLC pts receiving immune checkpoint inhibitor (ICI) monotherapy. Methods: This study retrospectively analyzed 232 pts with stage III/IV or recurrent NSCLC who initiated palliative ICI monotherapy (1 st line: 52, ≥2 nd line: 180) from September 2017 to August 2022 in a single center. TEE occurrences were confirmed in pts during ICI treatment or within 6 months post-completion, while TEEs after regimen change were excluded. Results: Pembrolizumab (107 pts) was the most frequently administered agent, followed by atezolizumab (63 pts) and nivolumab (62 pts). TEEs were identified in a total of 14 pts (6.0%), and pulmonary thromboembolism was the most common type of TEEs (7 pts). No significant risk factors associated with TEE occurrence were identified, including age, performance status, Khorana score, type of drugs, and the line of chemotherapy. Conclusions: TEEs occurred at a relatively lower incidence in NSCLC pts receiving ICI monotherapy compared to previous studies involving cytotoxic chemotherapy, particularly platinum-based regimens. Nevertheless, the incidence is non-negligible and careful monitoring for TEEs in NSCLC pts undergoing ICI monotherapy is needed.
Exploring the correlation between high HRD status and immunotherapy response in melanoma.
Authors: George Nassief, Tolulope Tosin Adeyelu, Alice Yao Zhou, Jesse W. Keller, Farah R. Abdulla, Ari M. Vanderwalde, Geoffrey Thomas Gibney, Soo J. Park, George Ansstas
Journal: Journal of Clinical Oncology (2024)

e21541 Background: Homologous recombination deficiency (HRD) status demonstrates DNA instability in tumor cells and has been implicated as a response marker for immune checkpoint inhibitors (ICI). Here, we explore the correlation between high HRD status and ICI response biomarkers, homologous recombination repair (HRR) mutations, and the prognostic advantage of high HRD status following ICI in cutaneous melanoma patients. Methods: Melanoma samples (N = 2158) were profiled for genomic loss of heterozygosity (LOH) by NGS at Caris Life Sciences (Phoenix, AZ). As a surrogate for HRD, LOH-high was defined as LOH at ≥ 16% of the segments analyzed (up to 552). PD-L1 expression was assessed using IHC (SP142; positive (+): ≥ 1%). Mismatch repair deficiency/microsatellite instability-high (dMMR/MSI-H) was tested by IHC/NGS.Tumor mutational burden (TMB)-high was defined as ≥ 10 mutations/Mb. interferon gamma (IFN-g) and T-cell inflamed scores. Real-world overall survival (rw-OS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from the start of immunotherapy until the last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied where appropriate, with p-values adjusted for multiple comparisons. Results: Melanoma patient samples include - cutaneous: 1853; acral: 130; mucosal: 175, with LOH-high observed in 8.3% of cutaneous specimens, 13.1% of acral, and 30.9% of mucosal. Firstly, most biomarkers associated with response to ICI (PD-L1, TMB-high, total neoantigen load, IFN-g score, T-cell inflamed level, and dMMR/MSI-H) were not significantly different between LOH-high and LOH-low cohorts in all melanoma subtypes. However, TMB-high was significantly more prevalent in LOH-low cutaneous melanoma patients (54.9% vs 63.3%, p = 0.039). Prevalence of HRR gene mutations was not significantly different between high and low LOH groups in all cohorts, except for the ATRX gene which exhibited a significantly higher prevalence in the high LOH cutaneous (8.6% vs 1.3%, p &lt; 0.001) and mucosal (28.8% vs 2.5%, p &lt; 0.00001) melanoma specimens. Analysis of rw-OS showed no improvement in the treatment of LOH-high cutaneous melanoma patients with ICI compared to LOH-low (HR: 1.397 [95% CI: 0.759- 2.569], p = 0.281). Conclusions: This study demonstrates that HRDness reflected by the high-LOH status in melanoma did not correlate with mutations in HRR genes. In addition, melanoma specimens with high HRD status did not exhibit an overall higher prevalence of biomarkers associated with ICI response. Our study did not demonstrate improved survival outcomes in patients with high HRD status following anti-PD1 therapies. Future investigation is needed to assess other therapeutic approaches for these patients such as PARP inhibitors.