bluuebunny/crossref_metadata_2025_split huggingface dataset:
A retrospective study of tislelizumab combined with bevacizumab, pemetrexed, and carboplatin in driver-gene mutated advanced non-squamous non-small cell lung cancer after tyrosine kinase inhibitors failure.
Authors: He Sisi , Ma Hu , Meng Mi , Tang Yang , Qu Wendong , Han Xu , Chen Cheng 
Published: July 2024

e20620 Background: Overcoming resistance to tumor targeted therapies is a major challenge in the management of driver-gene mutated non-small cell lung cancer (NSCLC). Recent clinical trials suggested that the combination approach of immunotherapy, bevacizumab and platinum-based chemotherapy was effective for driver-gene mutated NSCLC after tyrosine kinase inhibitors (TKIs) failure. Our retrospective study was aimed to examine the efficacy and safety of tislelizumab (TIS) combined with bevacizumab plus chemotherapy for advanced driver-gene mutated non-squamous NSCLC (nsq NSCLC) who had failed to TKIs therapies. Methods: We retrospectively collected medical records of driver-gene mutations advanced nsq NSCLC who had failed to TKIs therapies in the Affiliated Hospital of Zunyi Medical University and Second Affiliated Hospital of Zunyi Medical University from January 2021 to December 2023. The participants were sorted into two groups. Pts in TBCP group received TIS combined with bevacizumab, carboplatin and pemetrexed (BCP) for six cycles, followed by TIS with pemetrexed as maintenance therapy. Pts in BCP group received BCP regimen for six cycles, followed by pemetrexed as maintenance therapy. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), overall survival (OS) and safety. Results: A total of 12 pts were enrolled (6 pts in TBCP group and 6 pts in BCP group). In TBCP group, there was one patient with EGFR exon 19del, KRAS, BRAF V600 mutation and RET fusion, respectively. 2 pts harbored EGFR exon 21 L858R mutations. In BCP group, 4 pts harbored EGFR exon 19del, 1 patient with exon 21 L858R, and 1 patinet with BRAF V600 mutation. All pts were failed to previous TKI therapy. 3 pts (50%) had progression after two systemic treatment lines in ABCP group. 4 pts(66.7%) had progressive disease after at least two systemic regimen. As of 6 February 2024 (median follow-up, 18.6 months), significantly longer PFS was observed in TBCP group compared with BCP group (HR = 0.269 [95% CI: 0.068-1.065], p = 0.0080). Median PFS was 14.20 months (95% CI: 0.5010-5.379) and 8.65 months (95% CI: 0.1859-1.996) in TBCP group and BCP group, respectively. A higher ORR assessed was observed with TBCP group (66.7%) compared with BCP group (33.3%). The DCR were both 100% in two groups. Median OS was not reached. Grade 3-4 TRAEs occurred in 1 and 2 pts in TBCP group and BCP group, respectively. Conclusions: TIS combined with bevacizumab, carboplatin and pemetrexed has shown a promising anti-tumor efficacy with manageable safety profile for TKI failure driver-gene mutations advanced nsq NSCLC. However, these findings still need to be further confirmed by prospective clinical trials with larger sample sizes.
Immunotherapy in stage IV non-small cell lung cancer according to racial characteristics and community of residence.
Authors: Chang Annie , Untalan Matthew , Flores Raja Michael , Taioli Emanuela 
Published: July 2024

e20621 Background: Non-small cell lung cancer (NSCLC) remains the leading cause of cancer mortality worldwide. The advent of immunotherapy has transformed treatment paradigms for NSCLC. However, the use and effectiveness and immunotherapy may differ across racial groups and other sociodemographic factors, including sex, comorbidities, and community of residence. Our study analyzed disparities in immunotherapy receipt and overall survival among patients with stage IV NSCLC. Methods: Patients diagnosed with stage IV NSCLC from 2014 through 2016 were identified using the Surveillance Epidemiology, and End Results (SEER)-Medicare linked dataset. Immunotherapy receipt was compared across racial groups: non-Hispanic Whites, Blacks, Asians, Hispanics, and Native Americans. A multivariable logistic regression model evaluated associations between immunotherapy receipt and demographic and clinical variables including age, sex, marital status, Charlson comorbidity index, and histology. A multivariable Cox proportional hazards model assessed associations between these variables and overall survival. Results: Among 21,444 patients, the majority (78.6%) were White, while 10.7% were Black, 4.9% were Asian, 1.6% were Hispanic, and 0.2% were Native American. The efficacy of immunotherapy treatment was present across races, associating with better overall survival versus no immunotherapy (adjusted HR: 0.54, 95% CI: 0.49-0.59). After accounting for community of residence, race remained a significant factor in immunotherapy receipt (type 3 p-value: 0.028). Further adjustment for other covariates revealed that Black patients had significantly lower odds of receiving immunotherapy than White patients (adjusted OR: 0.64, 95% CI: 0.47-0.87). While Hispanics and Asians also had lower rates of receiving immunotherapy, these differences were not statistically significant. Asian patients exhibited higher overall survival compared to other races (adjusted HR: 0.88, 95% CI: 0.82-0.95). Conclusions: Use of immunotherapy for stage IV NSCLC is substantially lower among Blacks and other minority groups compared to Whites, indicating racial disparities in access to novel lung cancer treatments. Patients treated in urban areas are more likely to receive immunotherapy, underscoring the need to expand consistent access to efficacious treatments for advanced NSCLC. Ensuring equal access to effective treatments such as immunotherapy, regardless of race or community of residence, has the potential to improve outcomes and reduce racial disparities in lung cancer survival.
A medical school curriculum to foster the physician-patient relationship through narrative medicine.
Authors: Yao Johnathan , Hunter Cameron , Jaber Chehayeb Rachel , Sanft Tara B. , Prsic Elizabeth Horn , Dunne Dana , Kang-Giaimo Angela 
Published: July 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.
The impact of an inclusion council in an independent community oncology practice.
Authors: Fleming Mark T. , Lyons Kristina , Poole Roshonda , Richards Margot , Hepburn Sonia , Ali-Spencer Tahj , Lewis Tifany 
Published: July 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]
Case series: Outcomes of immunotherapy in locally advanced and metastatic cutaneous squamous cell carcinoma in Lakes and Waikato region.
Authors: Yogarajah Ahrabie , Wickham Alistair , Hari Dass Prashanth 
Published: July 2024

e21529 Background: Cutaneous squamous cell carcinomas (CSCC) have an incidence of 425 per 100,000 in New Zealand (1). 5% progress to locally advanced or metastatic disease. Immunotherapy is unfunded for this indication despite excellent response and safety profile (2). The objective was to evaluate real world outcomes of patients who managed to access immunotherapy. Methods: Review of referrals to medical oncology in the Lakes &amp; Waikato region between 1 August 2017 to 31 August 2022 with unresectable locally advanced or metastatic CSCC who had immunotherapy. Patients who were not referred to medical oncology, could not afford immunotherapy and/or unsuitable for a clinical trial were excluded from analysis. Results: 13/15 (86.7%) reviewed were male. Mean age was 71. 7 were locally advanced and 8 were metastatic. 14 self-funded pembrolizumab (11 first line, 3 second line). 1 accessed immunotherapy via a trial. 12 (80%) had significant responses; 3 achieved a complete response and 9 achieved a partial response. Median duration of response was not reached, with a median number of 18 cycles delivered. Median follow up was 23.8 months. 9 (60%) remain alive with ongoing response. 6 died on treatment; 3 from non-malignancy and non-treatment related causes. No Grade IV toxicities were observed. Grade III transaminitis was seen in one patient. Grade I-II toxicities seen in 11 (73.3%), including arthralgia (26.7%), fatigue (20%), transaminitis (13.3%), rash (20%), hypothyroidism (6.7%), diarrhoea (6.7%) and dyspnoea (6.7%). Conclusions: Despite an elderly & comorbid cohort, immunotherapy resulted in durable responses and excellent safety profile, highlighting the unmet need for immunotherapy funding in New Zealand. More understanding is required around the different responses to anti-PD1 therapies for the same malignancy type. (1) Pondicherry A, et al. The burden of non-melanoma skin cancers in Auckland, New Zealand. Australas J Dermatol. 2018 Aug; 59(3):210-213 (2) Hughes B, et al. Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 study): an open-label, nonrandomized, multicentre, phase II trial. Ann Oncol. 2021;32(10):1276-1285.
Examining the risk of immune checkpoint inhibitor-related toxicity among patients with melanoma and their history of cannabis use.
Authors: Waris Imtisaal , Raiker Rahul , Siva Nanda , Goswami Sanya , Pakhchanian Haig , Kamran Amir Shahzad 
Published: July 2024

e21539 Background: With cannabis use rising due to better availability for recreational and medicinal uses, there is a need for studies examining cannabinoids interactions. Immune Checkpoint Inhibitors have been increasing in popularity among metastatic cancer patients like those with melanoma. The biological impact of cannabis is mediated in part by the CB1 and CB2 receptors present in the endocannabinoid system that is present in the immune system. ICI therapy also targets the immune system through manipulating PD-1/PD-L1 receptors to induce cancer cell death. Therefore, concurrent cannabis use with ICI therapy could have potentiating effects on toxicities and negatively impact efficacy. There is limited information in the literature examining this and therefore the goal was to examine the impact of ICI toxicity risk among melanoma patients on any form of ICI therapy. Methods: A retrospective cohort study was conducted using TriNetX, a multicenter database comprised of ~100 million patients across 84 healthcare organizations. Adults ( > 17 years) from 2012-2023 were identified based on ICI-therapy initiation within 1 month of malignant melanoma diagnosis. Patients were then stratified by history of those with and without cannabis use disorder. ICI toxicity categories were determined a priori and included cardiac, nephrological, gastrointestinal, endocrine, respiratory, ocular, hematological, hepatological, musculoskeletal, and neurological toxicities. 1:1 propensity score matching was conducted to control for comorbidities and demographics. Adjusted hazard ratios (aHR) with 95% CI were calculated at 1-year follow-up after therapy initiation for ICI toxicities between the cohorts. aHR was estimated using the Cox proportional hazard model. Results: A total 14589 melanoma patients who underwent ICI therapy were identified where 2.3% had history of cannabis use. Matching revealed two balanced cohorts of 344 patients. Melanoma patients with a history of cannabis use did not have any significant differences with controls for cardiotoxicity (aHR[95%CI] = 0.94[0.54,1.6]), Nephrotoxicity (0.86[0.51,1.5]), GI toxicity (1.44[0.95,2.2]), endocrine toxicity (1.2[0.82,1.8]), respiratory toxicity (0.93[0.55,1.6]), ocular toxicity (0.63[0.25,1.6]), hematologic toxicity (1.04[0.7,1.6]), neurotoxicity (1.04[0.6,1.7]), liver toxicity (1.41[0.78,2.5]), or musculoskeletal toxicity (1.53[0.62,3.8]). Conclusions: With cannabis use rising due in part to recreational use and in part to medical marijuana, the implications of use must be a topic of research. Cannabis use among melanoma patients did not provide any significant differences in risk of developing ICI-therapy-related toxicities. Additional studies are needed to validate this finding.
CD44 and CD271 expression and chemoresistance in BRAF V600E/K mutation–positive melanoma.
Authors: Hyde Erin , Reed Madison J , Baer Robert W. 
Published: July 2024

e21542 Background: Melanoma stem cells (MSC) are thought to play a role in cellular proliferation, migration, and chemotherapeutic resistance. We investigated native expression of several putative MSC biomarkers in human BRAF V600E/K mutation positive melanoma cell lines of different phases—radial growth phase (WM35), vertical growth phase (WM278)—and metastatic (LM-Mel-45, LM-Mel-71) cell lines. We examined cell viability of select cell subpopulations during in vitro treatment with BRAF and MEK inhibitor monotherapy and combination therapy. Methods: Using flow cytometry, we assessed surface expression of putative MSC biomarkers: CD44, CD271, CD133, CD186, and CD20. We sorted each cell line by CD44 and CD271 expression with a predetermined hierarchical gating strategy and compared 4 chemotherapy conditions: control, BRAF inhibition with 1.25 µM dabrafenib, MEK inhibition with 0.125 µM trametinib, and combination therapy. Cells (25,000) were collected directly into chemotherapy treated media and incubated for 72 hours. Cell viability was measured by MTT assay. Statistical analysis used mixed-effects ANOVA and Tukey HSD. Results: No significant expression of CD133, CD186, or CD20 was found in any cell line. Over 99% of live cells were CD44+ in all 4 cell lines. Only WM35 and LM-Mel-71 had both CD44+/CD271+ and CD44+/CD271- subpopulations. CD271 expression was restricted to CD44+ cells. Among live cells, the CD44+/CD271+ subpopulation was 31.2% for WM35 and 14.4% for LM-Mel-71. For WM35, cell viability in CD44+/CD271+ cells was greater than CD44+/CD271- cells for all treatments (p < 0.001). For LM-Mel-71 cells, CD271 expression did not affect cell viability within any treatment (p = 0.64). For chemotherapeutic treatments, cell viability in CD44+/CD271- subpopulation was higher in LM-Mel-45 cells than WM278 (p < 0.03) or LM-Mel-71 (p < 0.002), but not WM35 cells (p > 0.05). Trametinib monotherapy and combination therapy had similar cell viability in all 4 cell lines (p > 0.05). Conclusions: To our knowledge, our study is the first to show differences in phenotypic expression of CD44 and CD271 across nonmetastatic and metastatic melanoma cell lines and suggests co-expression of CD44 and CD271 confers increased chemotherapeutic resistance to in vitro BRAF and MEK inhibitor treatment in radial growth phase but not metastatic melanoma. More research is needed to better understand the role of CD44 and CD271 co-expression in melanoma initiation, progression, and chemotherapeutic resistance. CD271 remains a potential immunotherapeutic drug target in the treatment of BRAF V600E/K mutation positive melanoma.
Peripheral blood biomarkers in immune checkpoint inhibition therapy in metastatic melanoma.
Authors: Ghelani Ghanshyam H. , Mandava Anupa , Bou Zerdan Maroun , Mehta Radhika , Sivapiragasam Abirami 
Published: July 2024

e21543 Background: Immune checkpoint inhibitors are extensively employed in the management of various solid cancers. Our study aims to assess the potential prognostic and predictive value of peripheral blood biomarkers, as well as their correlation with adverse events. Methods: In this study, we conducted a retrospective analysis of data retrieved from a cohort of 23 patients diagnosed with metastatic melanoma at a single institution between 2015 and 2019. Specifically, we focused on analyzing the neutrophil-to-lymphocyte ratio (NLR), absolute neutrophil+monocyte-to-absolute lymphocyte+eosinophil ratio (ANMC/ALEC) from complete blood count (CBC), and lactate dehydrogenase (LDH) level from peripheral blood to assess their correlation with progression-free survival (PFS), overall survival (OS), and immune-related adverse events (irAEs). Results: Our findings revealed that NLR values less than 0.34 and ANMC/ALEC ratio less than 3.45 were associated with improved PFS and OS, as well as a lower incidence of immune-related adverse events, which supports our initial hypothesis. However, these results were not statistically significant due to the low power of our study. On the other hand, high NLR values were significantly associated with higher pre-treatment LDH levels (P-value = 0.037), which is a well-established adverse prognostic factor in melanoma. Additionally, high ANMC/ALEC ratios were also found to be associated with high LDH levels, although this relationship was not statistically significant (P-value = 0.133). Conclusions: The results of our study suggest that patients with lower pre-treatment NLR and ANMC/ALEC ratios have better PFS and OS, as well as lower incidence of irAEs. Conversely, those with high NLR and high ANMC/ALEC ratios exhibited lower PFS and OS, as well as higher incidence of irAEs. High NLR and ANMC/ALEC ratios were also found to be associated with higher pre-treatment LDH levels, which have previously been demonstrated to be an adverse prognostic factor in melanoma. [Table: see text]