tbuckley/cabot-search huggingface dataset:
Anti-cancer activity of NTAX-44 (bioprocessed arsenic trioxide) on lung cancer.
Authors: Yogesh Narayan Bendale, Padma Shastry, Radha Pujari, Surendra Nagre, Nandinee Khot, Avinash Kadam
Journal: Journal of Clinical Oncology (2024)

e20573 Background: In contemporary allopathic medicine, intravenous administration of Arsenic trioxide is extensively investigated for its diverse applications in cancer treatment. However, the associated adverse effects demand exploration of alternative formulations. In present study, we propose the patented green technology-based compound “oral Arsenic Trioxide” (NTAX-44), in its unique form that can be administered orally, thereby reduces cost of treatment. This product presenting itself as a promising candidate for cancer therapy. Despite the ethnopharmacological uses of arsenicals in medicine, comprehensive understanding of their safety and efficacy remains limited. Thus, present study is proposed to investigate anticancer potential of NTAX-44 in lung adenocarcinoma cancer cell line A549. Methods: The effect of oral NTAX-44 was assessed on the viability of cell lines grown as 2D monolayers by MTS assay and 3D multicellular spheroid (MCS) model. Anti-metastatic potential of NTAX-44 was studied by using migration and colony formation assay while, expression of PD-L1 in A549 cell line treated with Arsenic Trioxide was checked by flow cytometry. The anti-metastatic capacity and cytocompatibility testing of Arsenic Trioxide was evaluated by in ovo chick embryo yolk sac membrane (YSM) angiogenesis assay and MTS assay using PBMCs respectively. Results: NTAX-44 is found to be effective to inhibit viability of A549 cell line (IC50 21.47±1.7 μg/ml for 48 hr and 14.65±0.92 for 72 hr of treatment); exhibiting its anti-proliferative activity. The A549 spheroids showed comparatively more resistance with loss of viability at higher concentration (50 and 100 µg/ml). Statistically significant decrease in scratch repair rate was observed at 24 hr and 72 hr of treatment and showing anti-migratory activity in A549 cells. In colony formation assay, complete inhibition of the colonization of A549 cells was observed after 48 hr of treatment; the survival fraction identified as 0%. NTAX-44 at 25µg/ml concentration inhibited PD-L1 expression in A549 cells, suggesting its potential to decrease expression of PD-L1 on tumor cells resulting in reversal of immune suppressive tumor microenvironment. Treatment of YSM with NTAX-44 resulted in approximately 40% inhibition in formation of quaternary blood vessels comparable to Bevacizumab (Avastin®). This significant anti-angiogenic potential is suggestive of its in vivo anti-metastatic effect. Notably, cytocompatibility testing of NTAX-44 at concentrations up to 200μg/ml was well-tolerated in PBMC cells emphasizing its favourable biocompatibility profile, providing crucial insights into its safety. Conclusions: Inhibitory effect of NTAX-44 on cell proliferation serves as a noteworthy attribute in context of its potential therapeutic utility against lung cancer. Its cytocompatibility further indicates application of arsenic trioxide as a candidate for clinical application.
A medical school curriculum to foster the physician-patient relationship through narrative medicine.
Authors: Johnathan Yao, Cameron Hunter, Rachel Jaber Chehayeb, Tara B. Sanft, Elizabeth Horn Prsic, Dana Dunne, Angela Kang-Giaimo
Journal: Journal of Clinical Oncology (2024)

e21015 Background: Narrative Competence is the ability to acquire, interpret and act on the stories of others.[1] Developing this skill can also improve health care practitioner’s sense of empathy and satisfaction with their work.[2] This study’s purpose is to evaluate the impact of a narrative medicine curriculum on medical students’ sense of connection to their patients and humanism in medicine. Methods: During the 2023 academic year, a narrative medicine assignment was introduced to the internal medicine oncology clerkship curriculum at the Yale School of Medicine. Third year medical students attended a training session on narrative medicine skills, interviewed a patient and wrote the patient’s story, and attended a session to read their written narrative. A survey was distributed to students asking for their reflections on the doctor patient relationship and the role of humanism in improving well-being and reducing burn out. Responses were de-identified and thematic analysis of responses was conducted. Results: 58 students participated in the training sessions and 11 (19%) completed a post-workshop free text survey with 5 questions reflecting on the doctor-patient relationship, the role of humanism in medicine, and the curriculum itself. Common themes that emerged include 1) how strong doctor-patient relationships makes medicine more meaningful, uplifting and enjoyable, 2) how seeking out a patient’s story is essential to the doctor-patient relationship and to optimal quality care, and 3) importance of doctor’s exhibiting care and sensitivity and placing diseases in context of their patients’ stories. Reflecting on the role of humanism in medicine, students reported that 1) taking the time to know your patients makes medicine rewarding, meaningful and worthwhile, 2) allows you to empathize and connect with patients more through recognizing their humanity and vulnerability and putting their frustrations in context, and 3) could be healing to both patient and provider. Further directions: Students suggested making the program mandatory, expanding to include pre-clerkship students and students on other clerkships, and providing more time and structure to facilitate interviewing patients and writing up their stories. Conclusions: A curriculum incorporating narrative medicine was effectively integrated and well-received by students and fostered an awareness of the rewards of listening to patient stories. References: [1] Charon R. The patient-physician relationship. Narrative medicine: a model for empathy, reflection, profession, and trust. JAMA. 2001;286(15):1897-1902. doi:10.1001/jama.286.15.1897; [2] Milota MM, van Thiel GJMW, van Delden JJM. Narrative medicine as a medical education tool: a systematic review. Med Teach. 2019;41(7):802-810. doi:10.1080/0142159X.2019.1584274.
Sex influence on cancer immunotherapy efficacy and safety in advanced non-small cell lung cancer (NSCLC): A Canadian institution real-world experience.
Authors: Sara Frida Cohen, Diane Cruiziat, Jeremy Naimer, Victor Cohen, Goulnar Kasymjanova, Alan Spatz, Jason Scott Agulnik
Journal: Journal of Clinical Oncology (2024)

e20618 Background: Males and females differ in innate and adaptive immune responses. This difference may also be reflected in their response to cancer immunotherapies. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment for advanced NSCLC, however the impact of sex on treatment outcomes in these patients remains unclear. The aim of this retrospective cohort study was to evaluate sex-related differences in immunotherapy outcome in a real-world population of NSCLC patients treated with ICIs. Methods: Demographics, clinical, pathological and treatment characteristics were assessed. Treatment-related variables were analyzed to understand the differences in efficacy and safety outcomes including response rates, PFS, OS and all-cause treatment discontinuation (TD) in relation to sex. Results: 152 advanced NSCLC patients receiving first-line immunotherapy, either alone or in conjunction with chemotherapy, were included in the study cohort. Females were younger age, were more likely to be non-smokers, have non-squamous tumors and had a higher prevalence of pre-existing autoimmune diseases compared to males. Disease control (CR/PR/SD) was achieved in 65.8% of patients. Median PFS was 12.0 mo in females and 14.1 mo in males. Median OS for all patients was 15.8 mo; 16.1 and 15.7 mo in females and males respectively. No statistical differences based on gender were observed in PFS and OS (P = 0.767 and P = 0.657). In regression analysis older age and presence of liver metastases were independent poor prognostic factors. Gender was not an independent prognostic factor in PFS and OS. Notably, 44 or 28.9% patients developed symptomatic immune-related adverse events (ir-AEs) that led to TD (Table 1). ir-AE-related TD occurred at a significantly higher rate in females compared with males (Table 1; 38.2% vs 19.7%, RR = 1.90; 95% CI: 1.12 to 3.26; p = 0.018). GI toxicity, including hepatitis and colitis was predominantly observed in females, whereas pneumonitis was the most frequent ir-AE leading to TD in males. Conclusions: Despite no significant differences based on gender were observed in PFS and OS, our study showed that female patients with advanced NSCLC receiving ICIs are at a substantially greater risk of severe symptomatic ir-AEs and TD. This finding indicates that broad-based sex differences in this context could potentially exist and emphasizes the need for further investigations into the role played by gender in immunity and cancer immunotherapy treatment.[Table: see text]
The impact of online CME on clinicians’ ability to utilize immunotherapy in unique populations of patients with NSCLC.
Authors: Michelle Arielle Worst, Andrew Small, Amy Furedy, Cong Zhang, Meng Yuan, Sukhbir Bahra, Stephen V. Liu, Jared Weiss
Journal: Journal of Clinical Oncology (2024)

e21004 Background: Immunotherapy (IO) has become a standard of care in the management of advanced non-small cell lung cancer (NSCLC). However, treatment with IO-based regimens may not always be straightforward, particularly in unique clinical scenarios and patient populations. As such, members of the multidisciplinary care team, including oncologists and pulmonologists, may lack experience in utilizing IO in these instances. The objective of this study was to assess the educational impact of a series of continuing medical education (CME) activities on the knowledge, competence, and confidence of oncologists and pulmonologists with respect to recognizing strategies that facilitate the safe and effective use of IO in patients with advanced NSCLC. Methods: The educational analysis consisted of 2 online, CME-certified activities. Educational impact was assessed with repeated pre-/post-education including multiple choice knowledge/competence questions and 5-point Likert scale confidence questions. Data from all oncologists and pulmonologists who completed pre- and/or post-education assessments were aggregated across activities and stratified by learning theme. Relative changes in percentage of correct responses and clinicians who were confident (value of 4 or 5) were used to measure improvement in knowledge, competence, and confidence. A McNemar’s test assessed significant levels of changes reported with P values &lt;.05 considered statistically significant. The first activity in the analysis launched October 2023 and the last launched November 2023; data were collected until January 2024. Results: The educational series resulted in improvements in oncologists’ (N=119) and pulmonologists’ (N=49) knowledge, competence, and confidence after education. Conclusions: This analysis demonstrates that oncologists’ and pulmonologists’ knowledge, competence, and confidence regarding the safe and effective use of IO in patients with advanced NSCLC improved after education. Despite these improvements, additional educational activities are needed to address residual gaps and further increase clinicians’ ability in these dynamic and challenging clinical settings. [Table: see text]
High dose bolus (HDB) interleukin-2 (IL2) and concurrent low dose ipilimumab followed sequentially by nivolumab in patients with advanced melanoma after failure of anti-PD1-based immunotherapy and BRAF-MEK inhibition.
Authors: Ahmad A. Tarhini, Zeynep Eroglu, Mariem Galuia, Islam Eljilany, Denise Kalos, Michael J Schell, Leticia Tetteh, Edith Abraham, Allison Richards, Andrew Scott Brohl, Nikhil I. Khushalani, Joseph Markowitz
Journal: Journal of Clinical Oncology (2024)

9543 Background: Options are limited for patients with advanced metastatic melanoma who have disease progression following anti-PD1-based immunotherapy and BRAF-MEK inhibition (if BRAF V600 mutant). Evidence supports synergism between IL2 and CTLA4 blockade in enhancing the immunogenicity of the tumor microenvironment and therapeutic susceptibility to PD1 blockade. Methods: We conducted a phase II study of HDB IL2 in combination with LD ipilimumab followed sequentially by nivolumab in patients with advanced inoperable stage III or stage IV melanoma with progression after anti-PD1-based immunotherapy and BRAF-MEK inhibitors. Treatment consisted of up to 3 courses (One cycle is 21 days and one course is 4 cycles). HDB IL2 and concurrent ipilimumab 1 mg/kg were given during week 1 of the initial 2 cycles of each course. Nivolumab was given during week one of the 3 rd cycle of each course. Patients without evidence of disease progression (RECIST v.1.1) or limiting toxicities (CTCAE v.5) were offered additional courses of treatment. A Simon two-stage minimax design (Simon, 1989) was followed. We report the outcomes for Stage I. Results: 12 pts (5 female, 7 male) with metastatic melanoma (2M1a, 1M1b, 6M1c, 3M1d) were treated. Median age 53 years (33 – 69), 11 cutaneous (including 1 acral) and 1 mucosal primary. Tumor mutation status: 4BRAF (V600E), 2NRAS (p.Q61K), 1NF1. The median number of prior regimens for metastatic melanoma was 3 (range 1 - 5). Eight patients previously received ipilimumab as monotherapy or in combination with anti-PD1. On study, the median number of doses of IL2 was 9 during cycle 1 and 7 during cycle 2. A median of 2 doses of ipilimumab and 1 dose of nivolumab were given as part of the combination regimen. Among the 11 evaluable patients (completed 1 course of systemic therapy), the response rate was 2/11 (18.2 %; 95% CI: 2.3% – 51.8%); 1CR, 1 PR, 5 SD, 4 PD and 1 NE as best response. After a median follow up of 39 months, both responses are ongoing (at 10+ and 37+ months), median progression free survival (PFS) was 3 months and median overall survival (OS) was 18.8 months. One-year PFS and OS were 17% (95% CI: 4.7% - 59%) and 83% (95% CI: 65% - 100%), respectively. The adverse event profile was consistent with the expected toxicity profile for each agent with no increase in frequency with the combination. Conclusions: Our combination regimen was relatively safe and well tolerated and demonstrated promising efficacy in a heavily pretreated patient population passing the prespecified efficacy criteria for Simon Stage I. The study has moved into Stage II testing. Clinical trial information: NCT04562129 .
The patient outcomes with EGFR-mutated advanced non-small-cell lung cancer receiving aumolertinib as first-line treatment.
Authors: Jisheng Li, Wen Zhao, Hongxin Li, Tiantian Xuan, Chengjun Wang, Rongyu Zhang, Chuang Yang, Jian Wang, Cuihua Yi
Journal: Journal of Clinical Oncology (2024)

e20619 Background: As a novel third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), aumolertinib demonstrated superior progression-free survival and a well-tolerated toxicity profile to gefitinib in front-line treatment of locally advanced or metastatic non-small cell lung cancer (NSCLC) in the AENEAS trial. However, the real-world impact of aumolertinib in the first-line treatment on patients' HRQoL still remains unclear. Methods: Advanced NSCLC patients with sensitizing EGFR mutations treated with aumolertinib 110 mg daily in the first-line treatment were prospectively enrolled and the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire C30 (QLQ-C30) and EORTC Quality of Life lung cancer-specific module (QLQ-LC13) information were collected. Efficacy evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.0 was also recorded here. Prespecified key symptoms were cough, hemoptysis, dyspnea, sore mouth or tongue, dysphagia, hair loss, tingling hands or feet, chest pain, arm or shoulder pain and pain of other sites. Results: Totally, 33 patients in the first-line treatment were included and 23 patients had efficacy information up to Jan 2024. The median follow-up time was 264 days (interval: 36-491 days). The objective response rate (ORR) and disease control rate (DCR) was 65.2% and 91.3%, respectively. All the patients haven’t reached the time to deterioration and the progression free survival(PFS) and overall survival is not reach. EORTC QLQ-LC30 showed general health status scale and functional scales increased and symptom scales decreased during aumolertinib treatment. Symptom scales assessed by EORTC QLQ-LC13 showed cough, sore mouth or tongue, chest pain, arm or shoulder pain and pain of other sites, were improved significantly after aumolertinib treatment (P &lt; 0.05). Conclusions: General health status, functional status and key symptoms improved from baseline in patients with advanced NSCLC receiving aumolertinib as first-line treatment. The ORR and DCR in our study was comparable in those showed the AENEAS trial.
Knowledge and confidence gaps in differentiating PARP inhibitors among community oncology providers.
Authors: Katie J.H. Robinson, Emily Scully, Kristin R. Rose, Robert A. Esgro, Nita Karnik Lee
Journal: Journal of Clinical Oncology (2024)

e21002 Background: Data and professional recommendations regarding the use of Poly(ADP-ribose) polymerase inhibitors (PARPis) for patients with ovarian cancer have evolved rapidly, challenging providers who manage patients with ovarian cancer (OC). Coupling confidence-based learning with continuing education (CE) is a proven tool to address such challenges towards enhanced patient care. Methods: A confidence-based continuing education (CE) activity was developed to address the evolving landscape of PARPi use in patients with OC. Pre-, intra-, and post-test assessment was used to quantify baseline parameters as well as the impact of education on knowledge and behaviors. The CME activity was available for credit from October 31, 2022 to October 30, 2023. Results: In total, 354 community oncology physicians or advanced practice providers (APPs) who see an average of 6 patients with OC per month completed the education. Baseline knowledge and confidence was low on topics related to strategies for molecular testing (29% correct) as well as the use of PARPis (27% correct). Moreover, on average, only 3% of those who answered correctly were confident in their response, highlighting a lack of confidence even in those who were correct. These knowledge and confidence gaps translated to only 24% of providers who use appropriate testing to determine BRCA1/2 and HRD status and only 16% feeling comfortable in differentiating PARPis. Additionally, while providers showed slight preference for olaparib in patients with homologous recombination deficiency (HRD) and niraparib in patients without HRD, on average 30% of providers were unsure of which agent to use in each clinical context. Overall, at baseline only 24% of providers reported individualizing the use of PARPis based on patient and tumor characteristics. Post-learning, there was a 46% increase in knowledge, and while the percentage of those who were confident and correct increased 21%, 76% remained unconfident. Still, these gains in knowledge and confidence resulted in two-thirds of providers making practice improvements in their use of PARPis, which resulted in improvements in patient health. Conclusions: The rapid evolution of the PARPi therapeutic landscape has caused gaps in knowledge, confidence, and behaviors. Ongoing and rapidly developed CE is a critical tool to address these challenges as data and recommendations for use continue to evolve rapidly.[Table: see text]
Lung cancer in females from nonsmoker families in India: Observations and inferences in 5 years.
Authors: Namratha Udupa M. S.
Journal: Journal of Clinical Oncology (2024)

e20610 Background: Incidence in lung cancer in last two decades has been changing drastically in terms of gender, age, smoking behaviour of patients, stage at presentation, histopathology, genetic abnormalities, operability at presentation and survival. More perplexing is the increase in its occurrence in females from non smoker families, mitigating the sole importance of the traditional risk factors of tobacco and smoking in the recent times. This highlights the need to investigate other risk factors like radon exposure from indoor pollution where females stay most of the time, exposure to arsenic and other chemicals in daily life, particle pollution, physical inactivity and inflammatory diseases of airways. Methods: It was an observational study of patients who were diagnosed and treated at a high volume cancer centre in Karnataka state of India. 89 never smoker female patients under 50 years of age from non smoker families with no obvious exposure to second hand or third hand smoke were enrolled from October, 2018 to June, 2023. It was a longitudinal prospective cohort study where the demographic data, symptoms with duration, histopathology including genetic abnormalities, treatment details and survival were noted. Results: 89 never smoker females from non smoker families with ages ranging from 36 to 50 years had a median age of 46 years. About 70% of the ladies were from houses closely associated with farm in past or present. 55% of them had overweight and obese body habitus. Most common presenting symptom was dry cough with median duration of about 3 months in about 89%. Other symptoms were pleuritic chest pain(39%), breathlessness (19%), generalized body ache(9%) and jaundice(2%). Stage of disease was IV(69%), IIIC(12.3%), IIIB(11.2%), IIIA(5.6%) and II in just one patient. Most common sites of metastasis were contralateral lung(45%), bone(20%), liver(20%), adrenal glands(10%) and brain (15%). Most common histopathology was adenocarcinoma(87.6%), adenosquamous carcinoma(7.8%), squamous cell carcinoma(3.3%), large cell neuroendocrine carcinoma in just one patient. EGFR was mutated in 56(62.9%) with deletion 19( 33%) and L858R(21%) being the most common abnormalities. ALK rearrangements and ROS1 fusion were seen in about 9(3.3%) and 3(3.3%) patients respectively. Surgery was done in only 3 patients and chemoradiation after neoadjuvant chemotherapy was given in 8(8.9%) patients. Median overall survival was about 42 months in stage IV patients. Conclusions: Changing demographic profile of lung cancer warrants more research into the other causes of lung cancer. More stage IV disease highlights the emphasis on prevention and screening for the disease.