bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic factors and long-term survivors in EGFR-mutated lung cancer: A multi-institutional retrospective analysis.
Authors: Kuan Feng-Che , Yang Yao Ren , Yuying Wu , Lin Meng-Hung , Shi Chung-Sheng 
Published: July 2024

e20594 Background: Evolution of tyrosine kinase inhibitors (TKIs) shapes the treatment paradigm of EGFR-mutated lung cancer, but resistance eventually develops. It is important to dissect the prognostic factors and to know the differences between long-term responders (LTR) and non-responders (NR). Methods: Electronic medical records were retrieved from Chang-Gung Medical Foundation from 2011 to 2020. Kaplan-Meier method was used to estimate survival, such as progression-free survival (PFS), and overall survival (OS). Multivariate Cox proportional hazard models was adopted to estimate adjusted hazard ratios and 95% confidence intervals. P < 0.05 was set to be statistical significance. Results: Totally, there are 3,551 patients receiving frontline TKIs, of which 825 (23.2%) are LTR with OS > 36 months, and 1,036 (29.2%) are NR with OS < 12 months. Besides, there are 1,200 (33.8%) LTRs with PFS > 18 months and 882 (24.8%) NR with PFS < 6 months. LTR tend to be younger, female, non-smoker, clinical stage 3b, no baseline brain metastasis, exon 19 deletions subtype, subsequent T790M development, bevacizumab usage, and osimertinib exposure (p all < 0.05). The median PFS of all enrolled patients is 12.3 months and median OS is 22.3 months. By multivariate analysis, age older than 65 years (Hazard ratio, [HR]:1.25 [1.15-1.36]), male (HR: 1.24 [1.13-1.36]), clinical stage 4 (2.19 [1.78-2.69]), baseline brain metastasis (1.25 [1.12-1.37]) are poor prognostic factors (p < 0.05). Also, T790M is not only predictive to osimertinib but also prognostic factor to OS (p < 0.05), and patients who developed subsequent T790M tend to have better PFS (18.1 v.s. 11.8 months). In patients without detected T790M along their disease course, exposure to osimertinib is related to better OS (33.1 v.s. 18.3 month, log-rank p < 0.05). Conclusions: LTR and NR are of distinctive characteristics, and T790M is prognostic and predictive to osimertinib. Further study is warranted for choosing the optimal treatment by clinical factors and T790M status.
First-line immunotherapy in patients with mNSCLC with rare molecular alterations.
Authors: Rossi Sabrina , Finocchiaro Giovanna , Lorenzi Elena , Masini Silvia , D'Argento Ettore , Toschi Luca 
Published: July 2024

e20604 Background: Oncogene-addicted non-small cell lung cancer (NSCLC) is an heterogeneous group including different molecular alterations. Most single agent (IO) and combination immunotherapy (CT-IO) trials excluded specific oncogene-addicted NSCLCs such as ALK and EGFR; however, it is likely that other oncogene driven tumours were not tested for but included in these trials and could be actually treated with IO in clinical practice. Methods: Among 428 patients treated with IO or CT-IO as first-line treatment, 30 patients were identified to harbour rare molecular alterations (37% non-smokers, 63% former or current smokers): METex14 skipping mutation (n = 10), MET amplifications (n = 4), BRAF other than V600E mutations (n = 7), HER2 exon 20 insertions (n = 5), RET fusions (n = 2), EGFR exon 20 insertions (n = 2). We analyzed progression-free survival (PFS) and overall survival (OS) in patients harbouring these mutations who underwent first-line IO (if PD-L1≥50%; n = 23) or CT-IO (if PD-L1 < 1-49% n = 2 or < 1% n = 5). Results: In whole population median PFS was 5,1 months (95%CI: 2,39-11,29) and median OS 25,5 months (95%CI: 8,80-60,98); 13 patients experienced progressive disease as best response, the disease control rate (DCR) was 56,7%. Patients treated with IO (n = 22) had a mPFS of 4,7 m (95%CI: 2,13-23,48) and a mOS of 29,8 months (95%CI: 10,08-60,98); those treated with CT-IO (n = 8) had a mPFS of 5,1 m (95%CI: 2,29-6,01) and a mOS of 8,5 m (95%CI: 7,68-12,51). Among the most represented molecular alterations, MET alterations (n = 14, 3 treated with CT-IO and 11 with IO) had a mPFS of 5,1 m (95%CI: 1,67-23,90) and a mOS of 25,5 m (95%CI: 8,80-60,72). In particular METex14 skipping mutations had a mPFS of 5,1 m and a mOS of 25,5 m, while MET amplifications had a mPFS of 2,4 m and mOS of 10,3 m. BRAF nonV600E mutations (n = 7, 2 treated with CT-IO and 5 with IO) had a mPFS 5,3 m and mOS not reached. HER2 exon 20 insertions (n = 5, 2 treated with CT-IO and 3 with IO) had a similar mPFS (6,0 m) but a poorer OS outcome (8,5 m). ( Table 1) Conclusions: Our results show a limited effectiveness of both IO alone and CT-IO as first-line treatment in oncogene addicted mNSCLC, even taking into account survival outcomes of upfront CT compared to targeted agents in pivotal trials. [Table: see text]
Safety and efficacy of osimertinib plus bevacizumab as first-line treatment in EGFR-mutant NSCLC with brain metastases: A dynamic ctDNA-guided study.
Authors: Wei Fang , An Juan , Hua Yichun , Ding Xiaosheng , Sun Shibin , Li Xiaoyan 
Published: July 2024

e20606 Background: Non-small cell lung cancer (NSCLC) patients with positive driver genes had a higher incidence of brain metastasis. This study evaluates the efficacy and safety of Osimertinib combined with Bevacizumab as first line treatment in EGFR-mutant NSCLC with brain metastases, utilizing liquid biopsy and dynamic molecular detection to guide treatment strategies. This approach is anticipated to bring progression-free survival (PFS) benefits and shows different resistant mechanisms. Methods: We enrolled EGFR-mutant NSCLC patients with brain metastases receiving Osimertinib and Bevacizumab as first-line therapy. Paired plasma and cerebrospinal fluid (CSF) samples were collected at baseline, during stable disease, and at disease progression for Next-Generation Sequencing (NGS) analysis. The study's primary endpoints were central nervous system (CNS) PFS and objective response rate (ORR). Secondary endpoints included overall PFS, ORR, disease control rate (DCR), and safety. We also investigated resistance mechanisms to the combination therapy. Results: A total of 28 patients from Beijing TianTan Hospital (May 2020 - July 2023) were retrospectively enrolled. The average Bevacizumab treatment duration was 8.21 months (range: 1-27 months). CNS PFS was 26.73 months (95% CI, not reached), and overall PFS was 21.93 months (95% CI, 18.84-25.02 months). The CNS PFS for patients with 19del and L858R mutations were not reached and 26.73 months (95% CI, 15.11-38.35 months), respectively (p = 0.25). Patients undergoing intracranial local treatment showed a CNS PFS not reached, compared to 23.33 months (95% CI, 16.21-30.45 months) for those who did not (p = 0.417). The CNS ORR was 88%, ORR was 76%, and DCR was 100%. At the time of data cutoff (Dec 15th, 2023), 1 patient progressed in both lung and CNS metastases, 8 patients only progressed in lung, 8 patients only progressed in CNS metastases .EGFR C797S mutation was detected in 2 plasma sample, Met amplification in 1 tumor tissue, EGFR C719S mutation in 1 paired plasma-tumor tissue and PIK3CA in 2 plasma sample. Increasing abundance in TP53 and CDKN2A were detected in 2 paired plasma-tumor tissue. Adverse events of grade 3 or higher included one case (3.6%) of severe ulcerative colitis leading to Osimertinib discontinuation and two cases (7.1%) of bevacizumab discontinuation due to bleeding events. Conclusions: Osimertinib combined with Bevacizumab as a first-line treatment significantly prolonged CNS PFS in EGFR-mutant NSCLC patients with brain metastases, offering superior control over intracranial lesions compared to Osimertinib monotherapy (15.2 months, FLAURA study). This study underscores the potential of dynamic ctDNA monitoring in guiding effective treatment strategies for this patient population. Further research is warranted to explore the broader clinical implications of these findings.
Unveiling disparities: Metastatic lung cancer incidence across income strata in metropolitan residencies.
Authors: Kenmoe Jerry , Akanbi Maxwell Oluwole , Amadi Nwonukwuru I , Olafimihan Ayobami Gbenga , Mikhail Elizabeth , Hrinczenko Borys 
Published: July 2024

e20616 Background: Over recent years, there has been growing interest in the field of lung cancer. Great efforts have been invested in recent years to improve screening and mortality outcomes with respect to lung cancer, particularly metastatic lung cancer (mLC). In the dynamic landscape of metropolitan residencies (MR), this study delves into the impact of household income (HI) on the occurrence of mLC. Unraveling the intricacies of these disparities is crucial for advancing our understanding of healthcare access and outcomes in urban settings. Methods: Appropriating data from the Surveillance, Epidemiology, and End Results (SEER) database, we looked at the incidence rates of mLC among adults aged 55-80 years by HI levels ( < $35,000, $45,000-49,999, $55,000-$59,999, $65,000-69,999 and $75,000+) in MR from 2004 to 2017. Age-adjusted rates were calculated, and joinpoint regression models were used to estimate the average annual percentage change (AAPC) in incidence across different subgroups. Results: The study population included a total of 321,281 individuals diagnosed with mLC. The incidence of mLC declined rapidly from 2004 to 2017 across all HI groups in metropolitan residence; the AAPC for HIs $45,000-49,999 was -0.70%, $55,000-59,999 was -2.11%, $65,000-69,999 was -4.32% and $75,000+ was -3.72%. Of note, there was not enough data to characterize the trend for HIs < $35,000. Conclusions: Our study revealed an overall decline in the incidence of mLC since 2004 across all HI groups in MRs. Although the trend is one of diminution across all groups, there is however, still some differences in incidence rates amongst different HI groups. This study elucidates the vital role HI plays in influencing the landscape of mLC in metropolitan areas. Recognizing and addressing these disparities is crucial for developing comprehensive public health strategies aimed at reducing the burden of advanced lung cancer and promoting equal access to quality healthcare.
Fostering collaborative care in multiple myeloma: The impact of holistic education on decision-making with antibody and CAR-T platforms.
Authors: Deluca Carmine , Beyer Michael , Ahlstrom Jennifer M. , Orlowski Robert Z. , Faiman Beth , Ghobrial Irene M. , Brugger Abigail , Drew Heather 
Published: July 2024

e21008 Background: The management of multiple myeloma (MM) continues to be transformed by evidence supporting the use of CD38 antibodies and B-cell maturation antigen (BCMA) immunotherapy (chimeric antigen receptor (CAR-T) and bispecific antibodies) in newly diagnosed and relapsed/refractory MM (NDMM and RRMM), respectively. However, real-world evidence and survey data show that these approaches are under-utilized across lines of therapy and that educational outreach to patients on their use is inadequate (Puig N et al. ASH 2022. Abstract 1859; Pink S et al. ISPOR 2022. Abstract HSD44; Terpos E et al. Blood Cancer J. 2021;11:40; Adu Y et al. ASH 2023. Abstract 2418). Methods: To address these gaps, PeerView partnered with HealthTree Foundation for Multiple Myeloma to develop 4 live events and 5 online enduring activities from 06/2022 to 06/2023, to educate clinicians on the evidence and principles for integrating CD38 and BCMA antibody platforms into patient care. The activities’ core objectives focused on improving knowledge and skills for integrating CD38 antibodies and BCMA immunotherapy platforms into sequential MM treatment. Furthermore, through the partnership with HealthTree Foundation, the initiatives featured patient perspectives as well as tools and resources to foster clinician–patient communication on use of antibody and CAR-T therapy. Pre- and post-activity multiple choice questions measured changes in knowledge and skills. Responses from enduring activity learners were compared with those from a matched sample of nonparticipants. In a meta-analysis of outcomes from the 9 activities, learning objectives were grouped by key themes, with changes in knowledge and skills averaged across them. Results: Total learners: 12,248 (hematologist-oncologists/oncologists: 7,345; oncology nurses: 1,247) In all activities, learners’ knowledge and skills improved, with increases of: 35 percentage points (ppt) in knowledge of new evidence and changing practice guidelines supporting BCMA antibody platforms in RRMM (44% to 79%); 36 ppt in skills in treatment planning and evidence-based integration of CD38 and BCMA-targeting antibodies in the management of MM (52% to 88%); 46 ppt in ability to address safety considerations related to the use of antibody therapy and BCMA immunotherapy (39% to 85%); 58 ppt in patient interaction skills (eg, counseling, shared decision-making) when using antibody-based and CAR-T platforms (28% to 86%). Conclusions: Improvements in knowledge and skills, combined with a greater focus on patient-centricity, suggest that learners are poised to more effectively integrate CD38 antibodies and BCMA immunotherapy into guideline-recommended MM care that improves the overall well-being and outcomes of patients with MM.
Temozolomide and nivolumab in patients with refractory metastatic melanoma (MM).
Authors: Quintos Jessica , Schellhammer Sophie , Ancell Kristin Kathleen , Johnson Douglas Buckner 
Published: July 2024

e21521 Background: Immune checkpoint inhibitors (ICI) are the standard treatment for patients (pts) with MM. However, only a subset of pts respond to ICIs. Temozolomide (TEM) is used in refractory settings but with low objective response rates and no clear overall survival benefit. The efficacy of combined ICI + TEM is not well described. Methods: This was a single center, retrospective study of pts with MM who received treatment with nivolumab (NIVO) and TEM or TEM alone between 11/6/2013 and 11/6/2023. Demographic information, disease characteristics, LDH, treatment, toxicity, objective response, and outcomes were collected. Results: 34 patients were included. 16 were treated with NIVO + TEM and 18 were treated with TEM alone. In the NIVO + TEM group, 81% were male (n = 13) with median age of 59.5 years (range 20-79), and in the TEM group, 56% were male with median age 61 (range 35-81). For NIVO + TEM, 31% had partial response (PR; n = 5), 6% had stable disease (SD, n = 1), and 63% had progressive disease (PD; n = 10). For TEM, 11% had PR (n = 2), 22% had SD (n = 4), and 67% had PD (n = 12) (p = 0.37). For NIVO + TEM, 2 PRs were durable, ongoing at 442 and 741 days; 3 PRs were transient (85-179 days); 1 pt had durable SD ongoing at 201 days. For TEM, PR durations were 173 and 504 days, and SD durations between 213-435 days. Five pts with PD treated with NIVO + TEM had mixed responses (31%) compared with 1 pt treated with TEM (6%). Median progression free survival (PFS) was 80 days (range 11-748) for NIVO + TEM and 55.5 days (7-415) for TEM (p = 0.31). Median overall survival (OS) was 160 days (43-363) for NIVO + TEM and 118 days (7-1938) for TEM (p = 0.15). There were 26 adverse events (AEs) for NIVO + TEM (27% grade 1, 42% grade 2, 19% grade 3, and 12% grade 4; thrombocytopenia and pneumonitis), and 25 AEs for TEM (40% grade 1, 40% grade 2, 12% grade 3, and 8% grade 4; thrombocytopenia) [p = 0.64]. Conclusions: NIVO + TEM occasionally produced durable responses, although outcome metrics were not clearly superior to TEM alone in this small study. Further studies should quantify the benefit of ICI + chemotherapy regimens in refractory MM. [Table: see text]
Treatment-free survival after immunotherapy discontinuation in advanced melanoma: A systematic review and meta-analysis of real-world studies.
Authors: Lu Ziyao Eric , Abbasi Muhammad Shahmir , Ephraim Adam , Hemphill Colton , Lapp Caroline , Kuznia Heidi , Afzal Muhammad Zubair , Shirai Keisuke 
Published: July 2024

e21523 Background: Immune checkpoint inhibitors (ICIs) have altered the treatment landscape of advanced melanoma with remarkable improvements in progression-free survival (PFS). Durable responses to ICI cessation have been shown in early clinical trials for ICI usage in melanoma, although the optimal duration of immunotherapy remains unclear. Treatment-free survival (TFS) after immunotherapy cessation for patients with complete response (CR), partial response (PR), and stable disease (SD) has been reported in real-world studies and may help to guide discontinuation of ICI therapy. Methods: A systematic search was conducted using PubMed, Embase, and the Cochrane Library to identify real-world studies reporting TFS after immunotherapy in advanced cutaneous melanoma patients with CR, PR, and SD at 12 and 24 months. Discontinuation due to iRAEs were included. Effect sizes were pooled using a random-effects model using the meta and metafor packages in R after logit transformation. Inter-study heterogeneity was quantified using I2 statistic. Results: Systematic review yielded 34 studies investigating TFS in prospective and retrospective studies. Of these, three retrospective cohort studies reported real-world TFS at 12 and 24 months. Overall, 738 patients with advanced melanoma were included in this meta-analysis, with 384 patients in CR, 278 patients in PR, and 76 patients in SD at time of ICI discontinuation. Mean patient age was 66.4 and 61.9% of patients were male. Pooled 12 and 24-month TFS proportions were higher for patients with CR than PR and for patients with PR than SD. Pooled 24-month TFS was statistically significantly greater in patients with CR compared to SD. I2 statistics showed considerable heterogeneity between studies ( > 80% in CR and PR subgroups). Conclusions: 12 and 24-month TFS after ICI discontinuation was significant for patients with CR and PR to therapy, suggesting the feasibility of ICI discontinuation in patients after therapy response. Pooled 12-month TFS for patients with SD was 66%, although with decline to 36% at 24 months. Limitations of this meta-analysis include a limited number of included studies. Further research is needed to determine the optimal duration of ICI therapy for patients with advanced melanoma depending on best overall therapy response. [Table: see text]
Characteristics of patients with metastatic malignant melanoma in Colombia: Results of the Epidemiologic Registry of Malignant Melanoma REMMEC ACHO.
Authors: Ospina Serrano Aylen Vanessa , Ortiz Diaz Juan David , Contreras Fernando , Munevar Isabel , Jimenez Paola , Mantilla William Armando , Idrobo Henry , Ramos Pedro , Manneh Kopp Ray , Arango Acevedo Natalia , Santa Daniel Andres , Rivas Tafurt Giovanna Patricia , Quiroga Alicia , Vargas Claudia , Yepes Andres , Alcala Castro Carmen Marcela , Lema Mauricio , Chinchia Isabel , Russi Noguera July Andrea , Triana Ivan Camilo 
Published: July 2024

e21530 Background: The features and prognostic factors of patients with metastatic malignant melanoma are not well established in our country. Our objective is to collect and analyze the characteristics of a cohort of Colombian patients. Methods: Analytical cohort study based on the Epidemiologic Registry of Malignant Melanoma in Colombia (REMMEC). Data were collected between January 2011 and December 2023. Patients older than 18 years with a confirmed diagnosis of advanced melanoma were included. Descriptive analysis of demographic and clinical characteristics and survival analysis using Cox regression and Kaplan-Meier models were performed. Results: 322 patients were included. Median age was 66.5 years (range 55-76), 56% (180) of patients were men, 87% (280) had advanced disease at diagnosis, most (82%) with non-brain metastases and 51% (164) with multiple organ involvement. Table 1. For first-line treatment, patients received single-agent immunotherapy (37.26%), doublet immunotherapy (10.25%), targeted therapy (9%), and chemotherapy (7.14%), while 29% received best supportive care BSC. In the second line, single agent immunotherapy 9.32%, targeted therapy (4.34%), doublet immunotherapy 3.42%, chemotherapy (5%) and 77% received BSC. In the third line, only 9% (29) of patients were able to receive any therapy. Median follow-up was 16 months (IQR 7-32), median progression-free survival (PFS) was 8 months (IQR 4-35) and median overall survival (OS) was 23 months (IQR 9-66). OS in the first-line setting with immunotherapy as monotherapy was 23 months (IQR 12-40) HR 0.40 P 0.035 and with doublet immunotherapy 16 months (IQR 8-28) HR 0.16 P 0.005 Clinical characteristics associated with lower median OS were brain metastasis (HR 1,95 P 0.001), ECOG 3-4 (HR 5,49 P 0.001) and multiple metastatic disease (HR 2,15 P 0.001). According to acral vs. non-acral histologic type, the median OS was 26 vs. 44 months, respectively (HR 1.30 P 0.26). Conclusions: In our cohort of patients with metastatic melanoma, we found clinical outcomes similar to those reported in the worldwide literature. It is necessary to continue the registry and follow-up of patients to identify specific prognostic factors. [Table: see text]
NRAS mutation in melanoma: Association of codon-specific changes on patient outcomes.
Authors: Mathew Thomas Vinay , Adeyelu Tolulope Tosin , Abdulla Farah R. , VanderWalde Ari , Park Soo J. , Russell Jeffery Scott 
Published: July 2024

e21545 Background: NRAS mutant melanoma is an aggressive subtype making up 20-30% of cutaneous melanoma cases without specific treatment options beyond immune checkpoint inhibition (ICI). Previous studies have suggested specific NRAS codon mutations are associated with unique signaling pathways. To test the hypothesis that NRAS codon mutations in cutaneous melanoma may drive a preferential response to ICI, we evaluated specific genetic subsets of NRAS mutant melanoma based on the Q61 and G12/G13 codons. Methods: Cutaneous melanoma samples (n = 4091) were analyzed by NGS at Caris Life Sciences. Samples were stratified by NRAS status and subdivided into NRASQ61, NRASG12/13, and NRAS-wildtype. PD-L1 expression was assessed using IHC (positive ≥ 1%). TMB-high was defined as ≥ 10 mutations/Mb. Transcriptomic signatures of MAPK pathway activation and T-cell signatures were calculated. Real-world overall survival (rwOS) information was obtained from insurance claims data, with Kaplan-Meier estimates calculated from time on ICI until last date of contact. Mann-Whitney U, Chi-square, and Fisher exact tests were applied as appropriate, with p-values adjusted for multiple comparisons. Results: Cutaneous melanoma samples were comprised of 22% NRASQ61 (n = 902), 3.1% NRASG12/13 (n = 125) and 74.8% NRASWT (n = 3064), with the most common NRAS mutation being Q61R. Patients harboring NRASG12/13 codon changes were associated with concurrent mutations in BRAF (21.0 vs 6.4%, p< 0.0001), NF1 (50.5% vs 8.7%, p< 0.0001), KIT (3.2% vs 0.2%, p< 0.001), ARID2 (22.1% vs 11.3%, p< 0.01), MAP2K1 (7.2% vs 2.6%, p = 0.022) compared to NRASQ61. NRASG12/13 tumors were more frequently TMB-high compared to NRASQ61 or NRASWT (83.1% vs 62.1% vs 55.1%, p = 0.0001), but no difference was observed in the prevalence of dMMR/MSI-H or PD-L1 expression. Transcriptomic analysis showed that NRASQ61 mutants had a significantly higher MPAS compared to NRASG12/13 or NRASWT cohorts (Median: 1.16 vs 0.67 vs 0.46, p = 0.0147), while T-cell-inflamed scores were significantly higher in NRASWT compared to NRASQ61 (Median: 4 vs -40, p = 0.00492) but not to NRASG12/13 (Median: 4 vs -13.5, p = 0.674). No difference in rwOS was identified in NRASG12/13 and NRASQ61 melanoma treated with ICI (HR: 0.753, [95% CI: 0.43 – 1.31], p = 0.316). Conclusions: Patients with NRAS-mutated cutaneous melanoma exhibit codon-specific ( NRASQ61 vs NRASG12/13) signaling and prevalence of immunotherapy-related biomarkers. Our findings indicate that melanoma samples with NRASG12/13 mutation tend to exhibit immune richness suggesting they could be viewed as a distinct group that might potentially benefit from immune therapies. This observation offers valuable insight into codon-specific tumor subsets, differential response to therapy, resistance mechanisms, and the potential development of combination therapies to enhance survival outcomes of patients with NRAS mutant melanoma.