Exploration of radiotherapy strategy for brain metastasis patients with driver gene positivity in lung cancer
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ABSTRACT:
SUBMITTER: Bi Q
PROVIDER: S-EPMC10905398 | biostudies-literature | 2024 Jan
REPOSITORIES: biostudies-literature
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Project description:Brain is the most common site of lung cancer metastasis, and the incidenceis are higher if patients have driver gene mutation. Patients with brain metastasis have a poor prognosis; further, different treatment methods affect the disease status and prognosis. In recent years, with the development of precision medicine, gradual progress has been made in treatments for lung cancer patients with brain metastasis, especially for those with driver gene mutations. This review first highlights the challenges of brain metastasis treatments, and then summarizes the research progress regarding targeted therapies for patients with driver gene mutation-positive lung cancer and brain metastasis. This review could help guide clinical decision making for individualized treatment in daily clinical practice.
| S-EPMC6885421 | biostudies-literature
Project description:BackgroundExtensive-stage small cell lung cancer (ES-SCLC) is a notoriously aggressive malignancy frequently associated with brain metastases (BMs), presenting substantial therapeutic challenges. This study delves into the effectiveness of immunotherapy combined with diverse radiotherapy, especially the influence of brain radiotherapy (BRT) on survival outcomes in the immunotherapy era.MethodsES-SCLC patients treated at Xiangya Hospital and Xiangya Boai Hospital from February 2020 to June 2024 were retrospectively included. The study focused on patients receiving immune checkpoint inhibitors (ICIs). Metrics included overall survival (OS) and progression-free survival (PFS), employing univariate and multivariate Cox regression models for statistical analysis.ResultsA total of 393 patients with ES-SCLC who received ICIs were included in the study. Within the entire cohort, the presence of baseline BMs did not statistically affect OS or PFS. However, thoracic radiotherapy (TRT) was identified as a favorable prognostic factor for both OS and PFS. BRT demonstrated a beneficial effect on OS across both the general cohort and the baseline_BMs subgroup. In patients from the baseline_BMs subgroup who had previously undergone TRT, ICIs plus BRT did not significantly improve OS compared to ICIs alone. Conversely, for patients who had not received prior TRT, adding BRT to ICIs significantly enhanced OS. Among the patients who underwent BRT, 71 received whole brain radiotherapy (WBRT) while 19 opted for stereotactic radiosurgery (SRS). No significant differences in OS and PFS were observed between the SRS and WBRT modalities. The sequence of ICIs relative to BRT was found to influence PFS adversely. Administering BRT before ICIs (RT-ICI) was associated with worse PFS compared to administering ICIs followed by BRT (ICI-RT). Additionally, no significant differences in OS and PFS were noted among the three subgroups defined by varying intervals between ICIs and BRT. For patients without baseline BMs, TRT and prophylactic cranial irradiation were associated with delayed onset of brain metastases.ConclusionsOur study underscores the importance of optimizing treatment strategies and considering the timing and integration of radiotherapy and immunotherapy to improve outcomes for patients with ES-SCLC, particularly those at risk of or presenting with BMs.
| S-EPMC11537770 | biostudies-literature
Project description:Brain metastasis, one of the common complications of lung cancer, is an important cause of death in patients with advanced cancer, despite progress in treatment strategies. Lung cancers with positive driver genes have higher incidence and risk of brain metastases, suggesting that driver events associated with these genes might be biomarkers to detect and prevent disease progression. Common lung cancer driver genes mainly encode receptor tyrosine kinases (RTKs), which are important internal signal molecules that interact with external signals. RTKs and their downstream signal pathways are crucial for tumor cell survival, invasion, and colonization in the brain. In addition, new tumor driver genes, which also encode important molecules closely related to the RTK signaling pathway, have been found to be closely related to the brain metastases of lung cancer. In this article, we reviewed the relationship between lung cancer driver genes and brain metastasis, and summarized the mechanism of driver gene-associated pathways in brain metastasis. By understanding the molecular characteristics during brain metastasis, we can better stratify lung cancer patients and alert those at high risk of brain metastasis, which helps to promote individual therapy for lung cancer.
| S-EPMC7848146 | biostudies-literature
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients. 28 brain metastasis samples: 19 from Marc Ladanyi 9 from William L. Gerald
| S-ECPF-GEOD-14108 | biostudies-other
Project description:Radiotherapy is one of the most commonly used treatment modality for brain metastases from lung cancer. Its use has evolved from conventional whole brain radiation therapy (WBRT) to more sophisticated stereotactic radiosurgery (SRS) and hippocampal sparing radiotherapy. Indications of cranial radiotherapy are also evolving with the advent of targeted therapies directed against molecular markers like epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK). Prognostic criteria such as recursive partitioning analyses and graded prognostic score helps in prognostication of brain metastases patients. Majority of the prospective and randomized studies of brain metastases from lung cancer have come from the developed countries with adequate resources. Efforts have been made to replicate or validate the data in developing countries. In this overview, we intend to discuss the role of radiotherapy for brain metastases in limited resource settings of developing countries. The aim should be to generate a good quality data which is applicable for routine clinical practice in a resource friendly manner. SRS is indicated in guidelines for limited brain metastases, however, it requires a more sophisticated treatment delivery and quality assurance machines which are not available at many centres in majority of the developing countries. Similarly, clinical research should be undertaken considering the demographic, clinical and genetic differences among different populations. Currently, tyrosine kinase inhibitors have dramatically changed the outcomes of metastatic non-small cell lung cancer including brain metastases. The role of WBRT is being questioned in driver mutated patients in developed countries. However, the applicability of this approach should be examined in resource constrained settings as availability of these drugs is limited, its higher cost and frequent use of surveillance brain imaging are the practical challenges.
| S-EPMC8182549 | biostudies-literature
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients. 28 brain metastasis samples: 19 from Marc Ladanyi 9 from William L. Gerald
2010-06-17 | E-GEOD-14108 | biostudies-arrayexpress
Project description:BackgroundThe suppressor of cytokine signaling 3 (SOCS3) is the negative feedback regulator of the JAK-STAT signaling pathway. The purpose of our study was to investigate the SOCS3 status in colon primary tumor and lung metastasis and its relationship with macrophages.MethodsThe SOCS3 expression pattern and its relationship with the immune response in pan-cancer was investigated using multiple methods. Samples and corresponding clinical information of 32 colon cancer patients with lung metastasis were collected, and the CD68, CD163, and SOCS3 status were conducted using immunohistochemistry (IHC). The relationship between SOCS3 status and macrophage markers was analyzed. Besides, we explored the molecular mechanisms of SOCS3 in lung metastasis via the TCGA database.ResultsHigh SOCS3 expression was more inclined to poor prognosis and was positively correlated with main immune cell infiltration in almost each cancer type, especially in colon cancer. Compared with the colon primary tumor, lung metastasis harbored higher CD163 and SOCS3 expression, and high SOCS3 expression was more likely to be associated with high CD163 expression in lung metastasis. Besides, the exceptional differentially expressed genes in lung metastasis significantly enriched in immune responses and regulations.ConclusionsSOCS3 possessed value as a prognostic marker and target for immunotherapeutic intervention in different tumors and might be a potential target of tumor progression and tumor immunotherapy in colon cancer.
| S-EPMC10070831 | biostudies-literature
Project description:Microarray analysis of 28 brain metastasis samples from lung adenocarcinoma patients.
2010-06-17 | GSE14108 | GEO
Project description:BackgroundA retrospective analysis verified the role of gene mutations in brain metastasis in patients with non-small cell lung cancer (NSCLC).MethodsData from 552 patients with advanced NSCLC treated from January 2015 to June 2017 in the Affiliated Cancer Hospital of Zhengzhou University were retrospectively analyzed. Next-generation sequencing was used to detect mutations in eight reported driver genes and various risk factors were evaluated.ResultsOf the 552 patients with advanced NSCLC, 153 (27.7%) had brain metastases. The univariate analysis showed that age (P = .008), gender (P = .016), smoking history (P = .010), lymph node metastasis (P = .003), and three driver genes, positive epidermal growth factor receptor (EGFR) mutation (P = .001), positive anaplastic lymphoma kinase (ALK) gene fusion (P = .021), and positive rearranged during transfection (RET) gene fusion (P = .003), were the factors influencing the incidence of brain metastasis. Logistic multivariate regression analysis revealed that positive EGFR mutation (P = .012), positive ALK gene fusion (P = .015), positive RET gene fusion (P = .003), pathological type (P = .009), lymph node N2-3 metastasis (P < .001), and a younger age (P < .001) were independent risk factors for brain metastasis. In addition, a receiver operating characteristic (ROC) curve was plotted with the above factors with an area under the curve = 0.705 (P < .001).ConclusionsAn EGFR mutation, ALK gene fusion, and RET gene fusion in advanced NSCLC patients play roles in brain metastasis as positive driver genes.ImpactAn EGFR mutation, and ALK and RET gene fusions are risk factors for brain metastasis in advanced NSCLC patients.
| S-EPMC6970058 | biostudies-literature
Project description:BackgroundWith the application of immune checkpoint inhibitors (ICIs) and the discovery of the synergistic effect of radiotherapy and immunotherapy, the intracranial benefit of thoracic radiotherapy (TRT) is receiving signiffcant clinical attention. The purpose of this study was to analyze the cranial benefits of ICIs and TRT in patients with extensive-stage small cell lung cancer (ES-SCLC) without baseline brain metastases (BMs).Materials and methodsFrom August 2019 to August 2022, data from patients diagnosed with ES-SCLC without baseline BMs were retroactively recorded. The Kaplan‒Meier method was used to calculate overall survival (OS), progression-free survival (PFS), and brain metastasis-free survival (BMFS), and the differences between the treatment groups were compared with the log-rank test. Risk factors associated with OS were analyzed via the Cox regression model.ResultsA total of 216 patients were included, with a median follow-up of 24.73 months. Among these patients, 137 (63.4%) received first-line ICIs combined with chemotherapy (ChT), including 32 patients treated with anti-programmed death 1 antibody (αPD-1) and 105 patients treated with anti-programmed death-ligand 1 antibody (αPD-L1), and 79 patients (36.6%) received first-line ChT alone. Compared with the ChT-alone group, the ICI + ChT group demonstrated significantly improved PFS (8.07 vs. 6.87 months; p < 0.001) and OS (19.83 vs. 13.80 months; p = 0.001). The addition of ICIs to the ChT regimen did not significantly delay the onset of BMs compared to that with ChT alone (16.93 vs. 12.67 months; p = 0.379). Notably, the addition of TRT to the αPD-L1 + ChT regimen significantly prolonged BMFS compared to that without TRT (20.27 vs. 8.80 months; p = 0.045).ConclusionIn patients with ES-SCLC without baseline BMs, first-line chemoimmunotherapy significantly improves PFS and OS. However, it does not delay intracranial metastasis. The addition of TRT to αPD-L1 + ChT therapy significant delays the development of BMs.Clinical trial numberNot applicable.
| S-EPMC11883939 | biostudies-literature