Lung Cancer, Год журнала: 2025, Номер 203, С. 108551 - 108551
Опубликована: Апрель 19, 2025
Язык: Английский
Cancers, Год журнала: 2024, Номер 16(6), С. 1174 - 1174
Опубликована: Март 17, 2024
Background: In patients with oligometastatic NSCLC, a cT3–cT4 primary tumor or an cN2/cN3 lymph node status was reported to be associated unfavorable outcome. The aim of this study assess the importance definitive neoadjuvant thoracic radiochemotherapy for long-term outcome these in order find more appropriate treatment schedules. Methods: Analysis West Cancer Centre (WTZ) institutional database from 08/2016 08/2020 performed. Patients synchronous OMD, all without actionable driver mutations, who received (RCT) RCT followed by surgery (trimodality treatment) were included. Survival is compared stage III NSCLC. Results: Altogether, 272 concurrent radiochemotherapy. Of those, 220 presented (158 RCT, 62 trimodality approach). A total 52 had OMD cT3/cT4 tumors. Overall survival (OS) at five years 28.3% (95%-CI: 16.4–41.5%), which not significantly different OS NSCLC treated (34.9% 27.4–42.8%)). However, PFS last follow-up worse than that (13.0% vs. 24.3%, p = 0.0048). latter due higher cumulative incidence distant metastases (50.2% 20.4% 48 months, < 0.0001) comparison patients. cross-validated classifier included severe comorbidity, ECOG performance status, gender and pre-treatment serum CRP level as most important factors univariable analysis, able divide patient group into two equally sized groups four-year rate 49.4% good prognosis 9.9% poor (p 0.0021). Laboratory chemistry clinical parameters, addition imaging high-precision therapies, can help predict improve prognosis. Conclusions: multimodality approach local metastases-directed therapy chemoimmunotherapy lead comorbidities therefore recommended.
Язык: Английский
Процитировано
5
Clinical Cancer Research, Год журнала: 2024, Номер 30(12), С. 2636 - 2646
Опубликована: Апрель 5, 2024
Abstract Purpose: The current National Comprehensive Cancer Network (NCCN) guidelines recommend afatinib or osimertinib as the preferred first-line treatment strategy for patients with advanced NSCLC harboring EGFR p.G719X mutation. However, in absence of head-to-head trials comparing p.G719X-mutant patients, it is unclear which regimen option. Experimental Design: A large cohort 4,228 treatment-naïve lung cancer who underwent targeted next-generation sequencing (NGS) testing was screened multicenter involving 68 and NGS profiling retrospectively enrolled to evaluate clinical responses (n = 37) third-generation EGFR-TKIs 31). Ba/F3 cells stably expressing p.G719A mutation were created investigate response vitro. Results: Concurrent p.E709X mutations, being most frequent co-occurring (∼30%), exerted a detrimental effect on outcomes treated EGFR-TKI [G719X/E709X vs. G719X; objective rate (ORR): 0.00% 47.62%, P < 0.001; mPFS: 7.18 14.2 months, 0.04, respectively]. Conversely, no significant difference found efficacy between p.G719X/E709X (G719X/E709X ORR: 71.43% 56.67%, 0.99; 14.7 15.8 0.69, respectively). In vitro experiments elucidated resistant drug sensitivity poor inhibition phosphorylation p.G719A/E709K upon treatment. Conclusions: Co-occurring mediated primary resistance but remained sensitive afatinib. personalized should be undertaken based coexisting status.
Язык: Английский
Процитировано
5
Опубликована: Май 3, 2023
The majority of EGFR mutations (85–90%) are exon 19 deletions and L858R point mutation 21, characterized by high sensitivity to EGFR-tyrosine kinase inhibitors (TKIs). Less is known about uncommon (10-15% mutations). Predominant types in this category include 18 mutations, 21 L861X, 20 insertions S768I. This group presents a heterogeneous prevalence, partly due the different testing methods presence compound mutation, which some cases leads shorter overall survival TKIs than simple mutations. EGFR-TKI may also vary depending on specific tertiary structure protein. best strategy remains uncertain data efficacy founded few prospective retrospective series. Newer investigational agents still under study there no other approved treatment targeting Defining option for patient population remain un unmet medical need. objective review evaluate existing outcomes, epidemiology clinical characteristics lung cancer patients with rare focus intracranial activity response immunotherapy.
Язык: Английский
Процитировано
10
medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Март 13, 2024
Air pollution significantly impact lung cancer progression, but there is a lack of comprehensive molecular characterization clinical samples associated with air pollution. Here, we performed proteogenomic analysis adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke primary contributor to high incidence. Genomic mutation revealed XWLC as distinct subtype LUAD separate cases smoking or endogenous factors. Mutational signature suggested that Benzo[a]pyrene (BaP) major risk factor XWLC. The BaP-induced hotspot, EGFR-G719X, was present 20% which endowed elevated MAPK pathway activations and worse outcomes compared common EGFR mutations. Multi-omics clustering identified four clinically relevant subtypes. These subgroups exhibited features biological processes, genetic alterations, metabolism demands, immune landscape, radiomic features. Finally, MAD1 TPRN were novel potential therapeutic targets Our study provides valuable resource for researchers clinicians explore prevention treatment strategies air-pollution-associated cancers.
Язык: Английский
Процитировано
4
Journal of Thoracic Oncology, Год журнала: 2024, Номер unknown
Опубликована: Июнь 1, 2024
Язык: Английский
Процитировано
4
Cancers, Год журнала: 2022, Номер 14(21), С. 5307 - 5307
Опубликована: Окт. 28, 2022
(1) Background: Afatinib has been approved for patients with non-small cell lung cancer (NSCLC) carrying major uncommon epidermal growth factor receptor gene (EGFR) mutations. Dacomitinib, another second-generation tyrosine kinase inhibitor, also shown promising potential EGFR However, no comparative study conducted. (2) Methods: Two cohorts were employed: the AFANDA cohort, an ambispective cohort including 121 mutations admitted to two tertiary hospitals in China, and external validation afatinib (ex-AC), extracted from Uncommon Mutations Database (N = 1140). The was divided into (AC) a dacomitinib (DC) internal exploration. Objective response rate (ORR), progression-free survival (PFS), adverse events (AEs) assessed comparison. Progression patterns resistance mechanisms explored. (3) Results: In total, 286 advanced NSCLC treated or enrolled, 79 (44 DC, 35 AC) 207 ex-AC. exploration, ORR of DC significantly higher than that AC (60.5 vs. 26.7%, p 0.008), but there significant difference median PFS between (12.0 months 10.0 months, 0.305). Multivariate analysis confirmed independent favorable effect on (hazard ratio (HR), 1.909; 0.047). validation, multivariate prognostic role (HR, 1.953; 0.029). Propensity score matching superiority over terms both univariate analyses. Toxicity profiling suggested more G1 (p 0.006), fewer G3 0.036) AEs AC. revealed incidence intracranial progression (50 21.1%, 0.002). Drug indicated occurrence T790M (11.8 15.4%, 0.772). (4) Conclusions: Compared afatinib, demonstrated activity manageable toxicity different
Язык: Английский
Процитировано
15
Journal of Pathology Informatics, Год журнала: 2023, Номер 14, С. 100298 - 100298
Опубликована: Янв. 1, 2023
In recent years, medical disciplines have moved closer together and rigid borders been increasingly dissolved. The synergetic advantage of combining multiple is particularly important for radiology, nuclear medicine, pathology to perform integrative diagnostics. this review, we discuss how subdisciplines can be reintegrated in the future using state-of-the-art methods digitization, data science, machine learning. Integration made possible by digitalization radiological images, as well pathological images. 3D histology become a valuable tool, not only integration into images but also visualization cellular interactions, so-called connectomes. human pathology, it has recently image calculate movements contacts immunostained cells fresh tissue explants. Recording movement living cell proving informative makes study dynamic connectomes diagnosis lymphoid tissue. By applying computational including science learning, new perspectives analyzing understanding diseases possible.
Язык: Английский
Процитировано
9
ESMO Open, Год журнала: 2024, Номер 9(6), С. 103592 - 103592
Опубликована: Июнь 1, 2024
•Largest dataset of NSCLC with uncommon EGFR alterations treated osimertinib.•Best outcomes compound uncommon–common mutations and G719X, L861X, or S768I.•Heterogeneous activity rarer mutations; no response at E709 residue.•Confirmed in the central nervous system, intracranial ORR 58%.•Amplification MET, TP53 mutations, E709K are putative mechanisms resistance. BackgroundOsimertinib represents standard care for treatment advanced non-small-cell lung cancer (NSCLC) harboring classical epidermal growth factor receptor (EGFR) constituting 80%-90% all alterations. In remaining cases, an assorted group (uEGFR) can be detected, which confer variable sensitivity to previous generations inhibitors, overall lower therapeutic activity. Data on osimertinib this setting limited strongly warranted.Patients methodsThe ARTICUNO study retrospectively evaluated data from patients uEGFR 21 clinical centers between August 2017 March 2023. analysis was carried out a descriptive aim. Investigators collected according RECIST version 1.1 criteria. The median duration response, progression-free survival (mPFS), were estimated by Kaplan–Meier method.ResultsEighty-six identified. Patients 'major' uEGFR, that is, S768I (n = 51), had rate (ORR) mPFS 50% 9 months, respectively. Variable registered cases 'minor' 27), 31% 4 Among seven exon 20 insertions, 14%, while best outcome among including least one mutation 13). Thirty presented brain metastases (BMs) 58% Amplification emerged after failure 18 available rebiopsy.ConclusionThe confirms especially those major even presence BMs. Alterations residue associated resistance osimertinib. Osimertinib warranted. method. Eighty-six rebiopsy.
Язык: Английский
Процитировано
3
Exploration of Targeted Anti-tumor Therapy, Год журнала: 2024, Номер 5(3), С. 742 - 765
Опубликована: Июнь 27, 2024
The management of lung cancer (LC) requires the analysis a diverse spectrum molecular targets, including kinase activating mutations in EGFR, ERBB2 (HER2), BRAF and MET oncogenes, KRAS G12C substitutions, ALK, ROS1, RET NTRK1-3 gene fusions. Administration immune checkpoint inhibitors (ICIs) is based on immunohistochemical (IHC) PD-L1 expression determination tumor mutation burden (TMB). Clinical characteristics patients, particularly age, gender smoking history, significantly influence probability finding above targets: for example, LC young patients characterized by high frequency rearrangements, while heavy smokers often have and/or TMB. Proper selection first-line therapy influences overall treatment outcomes, therefore, majority these tests need to be completed within no more than 10 working days. Activating events MAPK signaling pathway are mutually exclusive, hence, fast single-gene testing remains an option some laboratories. RNA next-generation sequencing (NGS) capable detecting entire repertoire druggable alterations, therefore it gradually becoming dominating technology diagnosis.
Язык: Английский
Процитировано
3
Опубликована: Окт. 2, 2024
Air pollution significantly impact lung cancer progression, but there is a lack of comprehensive molecular characterization clinical samples associated with air pollution. Here, we performed proteogenomic analysis adenocarcinoma (LUAD) in 169 female never-smokers from the Xuanwei area (XWLC cohort), where coal smoke primary contributor to high incidence. Genomic mutation revealed XWLC as distinct subtype LUAD separate cases smoking or endogenous factors. Mutational signature suggested that Benzo[a]pyrene (BaP) major risk factor XWLC. The BaP-induced hotspot, EGFR-G719X, was present 20% which endowed elevated MAPK pathway activations and worse outcomes compared common EGFR mutations. Multi-omics clustering identified four clinically relevant subtypes. These subgroups exhibited features biological processes, genetic alterations, metabolism demands, immune landscape, radiomic features. Finally, MAD1 TPRN were novel potential therapeutic targets Our study provides valuable resource for researchers clinicians explore prevention treatment strategies air-pollution-associated cancers.
Язык: Английский
Процитировано
3