tbuckley/cabot-search huggingface dataset:
J-TAIL-2: A prospective observational study of atezolizumab (atezo) combination therapy in patients (pts) with non-small cell lung cancer (NSCLC) in Japan.
Authors: Yasutaka Watanabe, Makoto Nishio, Kadoaki Ohashi, Atsushi Osoegawa, Eiki Kikuchi, Hideharu Kimura, Yasushi Goto, Junichi Shimizu, Eisaku Miyauchi, Hiroshige Yoshioka, Ichiro Yoshino, Toshihiro Misumi, Masafumi Yamaguchi, Kouzou Yoshimori, Masahiro Seike, Hironori Yoshida, Kazumi Nishino, Asako Miwa, Misa Tanaka, Akihiko Gemma
Journal: Journal of Clinical Oncology (2024)

8573 Background: The IMpower130 (West et al. Lancet Oncol 2018), IMpower132 (Nishio et al. JTO 2021) and IMpower150 (1) trials led to the approval of first-line atezo combination therapies for NSCLC. As data remain limited in Japanese pts, J-TAIL-2 (NCT04501497) is evaluating the efficacy and safety of 3 atezo combination therapies for NSCLC in the clinical setting in Japan. Methods: Japanese pts had unresectable advanced or recurrent NSCLC, were ≥20 y old, and were scheduled to start atezo combination therapy in clinical practice. Pts received atezo + carboplatin and nab-paclitaxel (atezo + CnP), atezo + carboplatin or cisplatin + pemetrexed (atezo + PP) or atezo + bevacizumab + carboplatin + paclitaxel (atezo + bev + CP). The primary endpoint was 12-mo OS rate. Secondary endpoints included OS and safety. Efficacy and safety were analyzed in the IMpower-unlike (did not meet the main eligibility criteria of each IMpower study) and IMpower-like subgroups. Geriatric assessment (G8) was done in pts ≥70 y old at baseline; a score &lt; median vs ≥ median indicated poorer health status. Results: From Aug 21, 2020, to data cut off (Feb 3, 2023), 814 pts were enrolled at 150 sites (atezo + CnP, n=217; atezo + PP, n=211; atezo + bev + CP, n=386). Baseline characteristics in the efficacy analysis population (n=791) are shown (Table). The IMpower-unlike group included pts with ECOG PS ≥2, brain metastases or interstitial lung disease. Twelve-mo OS rates (95% CI) were 62.9% (55.8, 69.2), 72.1% (65.2, 77.9) and 68.3% (63.2, 72.9), and median OS was 19.7, 23.5 and 17.3 mo with atezo + CnP, atezo + PP and atezo + bev + CP, respectively. OS HRs (95% CI) in the IMpower-unlike vs -like subgroups were 1.36 (0.91, 2.05), 1.08 (0.70, 1.68) and 1.49 (1.09, 2.06), respectively. The median G8 score for all evaluable pts was 13; in pts with a G8 score &lt; median vs ≥ median, OS HRs (95% CI) were 2.10 (1.22, 3.61), 3.53 (1.95, 6.37) and 2.04 (1.22, 3.40) with atezo + CnP, atezo + PP and atezo + bev + CP, respectively. In the safety analysis population (n=800), Grade ≥3 AEs occurred in 60.4% of pts and Grade 5 AEs in 1.3%. Conclusions: In Japanese pts, the efficacy and safety of each atezo combination therapy were comparable to those seen in the relevant IMpower studies and largely consistent in pts who would have been ineligible for the trials. Pts aged ≥70 y with a G8 score &lt; median vs ≥ median had poorer efficacy and safety outcomes. 1. Socinski et al. NEJM 2018. Clinical trial information: NCT04501497 . [Table: see text]
Germline NQO1c.559C&gt;T as a biomarker of genetic susceptibility to immune checkpoint blockade resistance.
Authors: Jose Carlos Benitez, Javier Oliver, Juan Luis Onieva, Manuel Cobo, Andres Mesas, Alberto Rios-Muñoz, Elisabeth Perez Ruiz, Maria Garrido-Barros, Paula Vazquez Rojas, Beatriz Martinez, Alexandra Cantero-Gonzalez, Andrea Gonzalez, Juan Zafra Martín, Isabel Barragán, Antonio Rueda Dominguez
Journal: Journal of Clinical Oncology (2024)

8537 Background: Tobacco is the main risk factor for developing lung cancer. Yet, some heavy smokers do not develop cancer while others do at young ages. The study of cancer immunology has led to the surge of immune checkpoint blockade (ICB), which transformed the treatment landscape of cancer pts. NQO1 has been associated with extreme phenotypes of high risk for the development of tobacco-induced NSCLC and with poor survival outcomes for xerographs. Development of biomarkers for ICB has been mainly focused on tumor-related factors while genetic susceptibility of the host has been poorly explored to date and some evidence suggests that genetic dysregulation may enables immune escape. Methods: From June 2016 to January 2023, 326 NSCLC pts from two main University Hospitals of Malaga (Spain) receiving ICB were prospectively enrolled, blood samples were gathered. We selected a representative set of 60 consecutive pts for exome sequencing to characterize the germline contribution to resistance (progression within the first 6 months of treatment). PBMC DNA was extracted and prepared for exome sequencing. Raw sequencing data was processed and aligned to a reference genome using BWA. Base recalibration, germline variant calling and variant filtering was performed through GATK. Survival probabilities were estimated with the Kaplan-Meier method and compared using the log-rank test. We explored the lung cancer related genes among our results. Results: Median age at diagnosis of 64 (54-85). 76,6% were men. 44/60 (73,3%) were adenocarcinoma (ADC), PD-L1≥1% in 55% of patients, 22% shown PD-L≥50%. 78% had advanced disease at diagnosis. 65% received ICB in combination with chemotherapy. We found NQO1c.559C&gt;T in 46,6% of pts (28/60). The variation was not associated with survival outcomes in the multivariant analysis (p&gt;0.05) but with poor OS for non-ADC histology (19.7m vs 6m for mutated and WT, respectively; p&lt;0.01). In addition, we found 26 germline variants associated with OS and PFS, and 52 variants with response to ICB. The variants were missense or involved a stop gain/loss. Conclusions: Exome sequencing analysis of germline variants could be a suitable methodology to identify subrogated biomarkers of immune resistance in NSCLC patients. NQO1c.559C&gt;T might help to identify poor prognosis non-ADC pts in the ICB setting.
Programmed cell death ligand 1 (PD-L1) inhibitors versus programmed cell death 1 (PD-1) inhibitors for the first-line therapy of extensive-stage small cell lung cancer: A propensity score-matched study.
Authors: Yaru Tian, Shuangqing Lu, Yulan Sun, Xiaoyong Tang, Zhuoran Sun, Ke Zhao, Guochang Du, Wanjing Li, Hui Zhu
Journal: Journal of Clinical Oncology (2024)

8086 Background: Addition of programmed cell death ligand 1 (PD-L1) inhibitors or programmed cell death 1 (PD-1) inhibitors to etoposide‐platinum (EP) chemotherapy has become the standard first-line regimen for ES-SCLC. The clinical efficacy and safety between the two types of immune checkpoint inhibitors (ICIs) remain controversial. We conduct the retrospective study and propensity score-matched analysis to explore the potential differences between them. Methods: Patients diagnosed with ES-SCLC and treated by EP plus PD-L1 or PD-1 inhibitors at Shandong Cancer Hospital between March 2019 and November 2022 were reviewed retrospectively. According to PD-L1 or PD-1 inhibitors, they were divided into two groups. Propensity score matching (1:1) was performed to balance the baseline characteristics of the two groups. The baseline characteristics and adverse events between the two groups were compared using the chi-squared test. The survival curves of overall survival (OS) and progression-free survival (PFS) were plotted by the Kaplan-Meier method and differences were analyzed by the log-rank test.The primary endpoints were OS and PFS. Results: As a result, 448 patients were analyzed in this study. 264 patients received PD-L1 inhibitors plus EP and 184 received PD-1 inhibitors plus EP. The median follow-up was 17.6 months. The median OS and PFS was 20.4 months and 7.8 months in the overall population. Before propensity score matching, the median OS was 20.1 months in PD-L1 inhibitor plus EP group and 20.7 months in PD-1 inhibitor plus EP group, respectively (HR 1.043, 95%CI 0.776-1.401; p= 0.781). The median PFS was 7.6 months in the PD-L1 inhibitor plus EP group and 8.5 months in PD-1 inhibitor plus EP group (HR 1.099, 95%CI 0.886-1.364; p= 0.390). After propensity score matching, the median OS and PFS were 20.4 months and 7.8months in PD-L1 inhibitor plus EP group, and those were 20.1 months and 8.6 months in PD-1 inhibitor plus EP group. There was no significant difference in OS and PFS between PD-L1 inhibitors plus EP and PD-1 inhibitors plus EP in the matched population (HR 1.104; p= 0.578 and HR 1.072; p= 0.602, respectively). The overall adverse events were comparable in the two groups. Only ≥3 grade neutropenia was more frequent in the PD-L1 inhibitors plus EP group (77.7% vs 69.0%, p= 0.040). Conclusions: In conclusion, the overall efficacy and safety profile was similar between PD-L1 inhibitors and PD-1 inhibitors for the first-line treatment of ES-SCLC.
Health insurance plans offered at NCI-designated cancer centers.
Authors: Vanessa Ann Moore, Jiazhang Xing, Max Joseph Bouvette, Anh B. Lam, Changchuan Jiang, Ryan David Nipp, Nirmal Choradia
Journal: Journal of Clinical Oncology (2024)

9052 Background: The health insurance landscape in the US represents an expensive and complex challenge to patients and physicians alike. Little is known about health insurance plans (HIPs) offered to physicians, particularly at NCI-designated cancer centers, which represent centers seeking to meet the highest standards. Methods: We collected data on the HIPs offered to physicians at NCI-designated cancer centers by reviewing institution websites from 11/2023 - 01/2024. We abstracted data on the insurance premium, deductible, out-of-pocket (OOP) maximum, and coinsurance for hospitalizations, limited to three HIPs per institution. We derived estimates using the lowest charge. We calculated inpatient stay costs based on standard hospital stay costs ($2,883 per day over an average of 4.5 days). We compared HIPs between public and private cancer centers. We used US Census Bureau population density data and regression models to explore associations among population density and OOP costs. Results: Among 65 NCI-designated cancer centers reviewed, 61 (93.8%) had readily available information about HIPs provided. Most institutions provided HIPs for all hospital employees, while 2 institutions only covered physicians. On average, each cancer center offered 3.67 HIPs, involving 1.67 insurers (54.1% offered a single insurer). Among 153 HIPs overall, 51.6% were preferred provider organization (PPOs) and one-third (33.3%) were health maintenance organization (HMOs). Only 22.9% of HIPs were high-deductible health plans (HDHP). The majority of cancer centers offered PPO plans (75.4%), HMO plans (57.4%), HDHP plans (55.7%), and some (24.6%) offered other plans, such as point of service and exclusive provider organization. Average costs for different kinds of HIPs are presented in the Table. A higher percentage of public cancer centers provided HMOs (60.5% vs. 50.0%, p=0.76) and PPOs (84.3% vs. 60.5%, p=0.09) than private centers, yet differences did not reach significance. Centers located in regions with higher state population density were more likely to have higher HMO OOP costs (beta=2.72; p=.006) and lower PPO OOP costs (beta=-2.98; p=.012). Conclusions: We found that most NCI-designated cancer centers had readily available information about HIPs provided to physicians. For these centers, physicians had limited HIP options offered, particularly in private institutions, which offered fewer HMO and PPO plans. We also demonstrated associations among state population density and OOP max in HMO and PPO plans. Our study provides a current synopsis of HIPs and identifies disparities among them, contributing to a foundation for future research. [Table: see text]
Hematology/oncology fellowship programs’ instagram presence.
Authors: Max Greenberg, Paddy Ssentongo, Shivani Mattikalli, Emily Tomasulo, Parth Anil Desai, Stuthi Perimbeti, Takefumi Komiya, Kevin Rakszawski
Journal: Journal of Clinical Oncology (2024)

9047 Background: Since the SARS-CoV-2 pandemic, applicants and programs have transitioned to virtual platforms as a surrogate for in-person visits. Social media provides insight into trainees’ experiences, wellness, medical education, and life outside the hospital. Instagram has been reported as the preferred platform and a majority of applicants note that social media content could change their perception of a program. 1 Due to the emergence of social media in fellowship recruitment, no studies have analyzed the relationship between Instagram content and hematology/oncology fellowship programs’ perception. Methods: The American Medical Association Fellowship and Residency Electronic Interactive Database was used to identify and categorize programs as either community-based (CB), community-based academic affiliated (CBAA), university-based (UB), military, and other. For programs with Instagram pages created prior to 2023, the posts from 2022 were subjectively classified into one of two categorizes, either “Medical Education” or “Fellow Life” based on the emphasis of the caption and image. “Medical Education” encompassed posts that promote education as well as academic accomplishments of trainees and faculty. “Fellow Life” included posts emphasizing culture, wellbeing, camaraderie, and social activities. Post from 2023 were analyzed for Instagram accounts created after 2022. The first image was used for posts containing multiple images. This was exempt from IRB review by Pennsylvania State University. Results: There are 183 accredited hematology/oncology fellowships programs; 60% (n=110) UB, 28% (n=52) CBAA, 9% (n=16) CB, 2% (n=4) others, and 0.5% (n=1) military. Of the 183 programs, 33 Instagram pages representing 18% of programs were identified (binomial test, p&lt;0.0001), consisting of 70% (n=23) UB, 24% (n=8) CBAA, and 6% (n=2) CB. UB programs were significantly more likely to have an Instagram (Fisher’s exact test p&lt;0.0001). Posts highlighting “Fellow Life” were significantly more frequent than those emphasizing “Medical Education” (Wilcoxon signed rank test, p = 0.001) (interquartile range: 65% (50-84%) vs. 36% (17-50%)). Conclusions: Despite the implementation of virtual interviews, an overwhelming majority of hematology/oncology fellowship programs do not have an Instagram page. Those with Instagram emphasize extracurricular wellbeing and culture, which is likely valuable to applicants. In this digital age, Instagram is not just a platform; it is a catalyst for connection, engagement, and decision-making in the hematology/oncology recruitment landscape. We advocate for a strategic embrace of Instagram, a balanced content mix highlighting academic and cultural facets, as a key recruitment strategy, reflecting the unique ethos of each program. Reference: 1. Oliver MG, Kelly K: Student Perceptions and Use of Social Media as Residency Program Information. Fam Med 54:380–383, 2022.
<i>IGF</i>-<i>1R,</i> E-cadherin, N-cadherin, and occludin gene expression and resistance to <i>EGFR</i> tyrosine-kinase inhibitors in patients with lung adenocarcinoma in Serbia.
Authors: Vera Jokic, Milena Cavic, Jelena Spasic, Mladen Marinkovic, Katarina Savic Vujovic, Radmila Jankovic, Bojan Zaric
Journal: Journal of Clinical Oncology (2024)

8524 Background: Mutations in epidermal growth factor-receptor ( EGFR) are found in approximately 10% of patients with lung adenocarcinoma in Serbia. EGFR tyrosine-kinase inhibitors ( EGFR-TKIs) is a safe and effective targeted therapy. However, most patients develop resistance. Acquired resistance to EGFR-TKI is defined as disease progression after achieving response or stable disease and there is a possible molecular association with epithelial-mesenchymal transition (EMT), particularly N-cadherin, E-cadherin, occludin and insulin-like growth factor-1 receptor (IGF-1R). We assessed the gene expression levels of IGF-1R, E-cadherin, N-cadherin, and occludin as predictive factors of resistance to EGFR-TKIs and survival outcomes in patients with advanced EGFR mutation-positive lung adenocarcinoma in Serbia. Methods: 101 patients with stage IIIB/IV EGFR mutation positive lung adenocarcinoma treated with EGFR-TKIs were included in the study. Quantitative RT-PCR was performed to determine mutations in EGFR, and expression of N-cadherin, E-cadherin, occludin and IGF-1R. Kaplan-Meier method was employed to estimate overall-survival (OS) and progression-free survival (PFS), with significance set at p&lt;0.05. Results: Median age of patients was 61.7 (39 - 81) years, 65.3% were females and 91% were diagnosed with metastatic lung adenocarcinoma. EGFR mutations were more frequently detected in females (p &lt;0.001). Median overall survival (OS) was 21 months (15.2–26.7 CI 95%) and progression-free survival (PFS) was 10 months (7.4-12.5 CI 95%). Patients whose tumors had lower levels of IGF-1R, and N-cadherin expression had statistically significantly longer PFS (p &lt;0.001). Patients with lower levels of IGF-1R and higher levels of E-cadherin gene expression were more likely to have a complete or partial response to therapy (p = 0.04). There was a statistically significant association between elevated IGF-1R expression and the occurrence of EGFR-TKI resistance in patients (p &lt;0.001). There was a statistically significant association between increased N-cadherin expression and reduced E-cadherin expression with EGFR-TKI resistance in patients. Conclusions: The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin. In this group of patients, higher levels of IGF-1R and N-cadherin gene expression were associated with shorter PFS and resistance to EGFR TKI, compared to higher levels of expression of E-cadherin, which may indicate potential value of expression of these genes in predicting acquired resistance to EGFR-TKI. Therefore, more research is needed to prove the potential predictive value of E-cadherin, N-cadherin and IFG-1R in acquired resistance to EGFR-TKI and developing novel therapeutic options with anti-EMT properties that can overcome this problem.
Impact of maintenance pemetrexed cessation on clinical outcomes of patients with metastatic non-squamous NSCLC.
Authors: Shreya Bhatia, Wade Thomas Iams, Matthew Lu, Spencer Lessans, Michael Libre
Journal: Journal of Clinical Oncology (2024)

8568 Background: Combination chemoimmunotherapy including pemetrexed and a PD(L)1 inhibitor is a common first line systemic approach for patients with metastatic non-squamous non-small cell lung cancer (NSCLC). Patients often discontinue maintenance pemetrexed due to adverse effects, and little is known about the impact of maintenance pemetrexed cessation on progression free survival (PFS) and overall survival (OS). Methods: 121 patients with stage IV or recurrent, metastatic non-squamous NSCLC treated at VUMC were included in this retrospective analysis. Patients diagnosed between 7/2017- 9/2023 were included if they received maintenance pemetrexed and pembrolizumab. Patients were divided into two groups: those who stopped pemetrexed due to toxicity and those who did not. PFS and OS were measured from time of stage IV or metastatic diagnosis to the date of radiographic progression or death, respectively, and compared with the Kaplan Meier method. Results: Among patients with stage IV or recurrent, metastatic NSCLC (n = 121), who remained on maintenance pemetrexed and pembrolizumab (n=68), the median PFS was 11.7 months (95% CI, 7.47-NA) compared to 24.3 months (95% CI, 19.4-NA) among patients who stopped maintenance pemetrexed (n=53; p=0.1). The median OS in the same patient groups was 25.8 months (95% CI, 13.8-NA) compared to 36.4 months (95% CI, 26.9-NA) (p=0.15), respectively. Among patients with stage IV disease at diagnosis (n = 97), the median PFS among patients who did not stop pemetrexed was 8.7 months (95% CI, 7.2–NA) compared to 24.3 months (95% CI, 17.3-NA) for patients who stopped pemetrexed (p=0.089). The median OS in these groups were 21 months (95% CI, 13.6-NA) and 38.6 months (95%, 28.0-NA) (p=0.054), respectively. Conclusions: In this study of patients with metastatic non-squamous NSCLC who received maintenance pemetrexed and pembrolizumab, patients who stopped pemetrexed due to toxicity experienced similar outcomes to those who continued with pemetrexed. The necessity of continuation of maintenance chemotherapy should be further evaluated in the immunotherapy era. [Table: see text]
The role of social media and email in hematology oncology fellowship program recruitment: Insights from national survey of program directors.
Authors: Rahul Kumar Thakur, Charan Thej Reddy Vegivinti, Hasiya Yusuf, Barun Ray, Rajvi Gor, Abhishek Kumar
Journal: Journal of Clinical Oncology (2024)

9049 Background: In the dynamically evolving medical landscape, the role of digital communication, encompassing both social media and email, in Hematology Oncology fellowship recruitment is increasingly prominent. This comprehensive study investigates how U.S. program directors (PDs) leverage these platforms, particularly in an era where virtual interviews are becoming the norm. By examining the utilization of social media alongside traditional email communications, this research aims to illuminate the dual strategies employed in engaging prospective fellows. Methods: From November to December 2023, a nationwide anonymous survey was conducted among all American Council for Graduate Medical Education (ACGME) accredited Hematology Oncology fellowship PDs. This survey sent via SurveyMonkey sought to collect demographic information of PDs, details about their programs, and insights into their use of social media platforms such as Twitter/X and Instagram, in addition to email, for both promoting their programs and reviewing fellowship applications. Results: In a survey of 183 Hematology Oncology fellowship programs, 32 program directors (PDs) responded, yielding an 18% response rate. The majority of PD were women (59%) with a predominant affiliation with university hospitals (69%). The responses indicated a broad geographical spread, especially in the South Atlantic and Pacific regions. Around 31% (10) of the program directors reported using Twitter/X, and 16% (5) utilized Instagram for promoting their fellowship programs. However, it was rarely used for applicant review (10% for Twitter/X, 0% for Instagram). Notably, there was no statistical difference in social media usage between university and community hospital PDs for program promotion or applicant engagement In contrast, email remains central in the recruitment process. On average, each PD receives about 57 emails expressing interest in their program. A considerable 71% (22) of PDs indicated that they would review an applicant who contacted them via email, with an average review rate of 80%. However, a relatively small percentage—18%—of the applicants reviewed were subsequently invited for an interview. Significantly, PDs from university hospitals were more inclined to review applicants via email compared to their counterparts in community hospitals (P-value&lt;0.01). Conclusions: This survey sheds light on the evolving dynamics of Hematology Oncology fellowship recruitment, marking a significant transition in the way program directors connect with potential candidates. Our research reveals that social media is gradually becoming part of the promotional toolkit for fellowship programs, yet email remains the primary method for communicating with and reviewing applicants.