Clinical Value of Upfront Cranial Radiation Therapy in Osimertinib-Treated Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer With Brain Metastases

Yu, Fan; Ni, Jianjiao; Zeng, Wenhui; Zhou, Yue; Guo, Tiantian; Zeng, Yue; Zhao, Yupei; Li, Shuyan; Li, Yida; Yang, Xi; Zou, Liang; Wang, Shengping; Liu, Quan; Li, Yuan; Chu, Li; Chu, Xiao; Ye, Luxi; Wen, Yu; Zhu, Zhengfei

doi:10.1016/j.ijrobp.2021.05.125

Cited by 25 publications

(38 citation statements)

References 37 publications

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“…In clinical practice, patients with oligo-BM (1-3 or 1-5 BM) are eligible for SRS, while WBRT is usually applied to patients with multiple BM. Recent research revealed that upfront SRS could bring survival benefits for patients with oligo-BM in the era of osimertinib; however, prescribing WBRT in advance failed to demonstrated such advantages [ 34 , 35 ]. Nonetheless these studies were mainly focused on patients with EGFR-mutated NSCLC, whereas no related research has been reported in ALK+ NSCLC.…”

Section: Discussionmentioning

confidence: 99%

Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Zou

Xing

Hao

et al. 2022

BMC Med

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Background Central nervous system (CNS) metastases in patients with ALK-positive non-small cell lung cancer (NSCLC) are a cause of substantial morbidity and mortality. Although alectinib had demonstrated promising intracranial efficacy in several clinical trials, data were limited on its CNS activity in real-world settings. Methods In this retrospective study, ALK-positive NSCLC patients with brain metastases (BM) or leptomeningeal metastases (LM) from six hospitals in China were divided into three cohorts based on the treatment history before the administration of alectinib. ALK-TKI-naive patients were enrolled in cohort 1, cohort 2 included patients who experienced intracranial progression with or without extracranial progression after treatment with crizotinib, and cohort 3 included patients who developed progression only in CNS following treatment with other second-generation ALK-TKIs. The definition and evaluation of intracranial and extracranial lesions were based on Response Evaluation Criteria in Solid Tumors version 1.1. Results Sixty-five patients were eligible and included in our study (cohort 1: 20, cohort 2: 32, cohort 3: 13). For the overall population and patients with uncontrolled CNS metastases, similar intracranial response in CNS target lesions was observed: cohort 1: 81.8% and 80%; cohort 2: 76.5% and 86.7%; cohort 3: 42.8% and 33.3%. For patients in these three cohorts, 75% (6/8), 78.6% (11/14), and 83.3% (5/6) were reported to have significant improvement in CNS-related symptoms respectively. The number of patients who were in need of mannitol or corticosteroids decreased remarkably after the treatment of alectinib (p < 0.001), and there was also a steep fall-over in the number of patients with ECOG ≥2 points before and after the administration of alectinib (p = 0.003). All patients (8/8) diagnosed with LM ± BM experienced substantial alleviation in CNS-related symptoms. In cohort 1 and cohort 2, no significant difference in CNS-time to progression was found between patients with symptomatic or asymptomatic BM when treated with alectinib alone. Conclusions Our study substantiated the potent CNS activity of alectinib in real-world settings. Patients with symptomatic and asymptomatic BM could benefit from alectinib comparatively, which indicated that alectinib alone might defer the timing of local treatment. However, our results should be treated cautiously owing to limited sample size.

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Section: Discussionmentioning

confidence: 99%

Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Zou

Xing

Hao

et al. 2022

BMC Med

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“…Although retrospective data evaluating first-generation EGFR-TKIs suggested that upfront radiotherapy improved the survival over TKI alone, 160 recent reviews and retrospective analyses in EGFR and ALK-positive NSCLC brain metastases support that upfront CNS-penetrating TKIs do not negatively impact outcome and that local radiotherapy may be deferred. [161][162][163][164] Furthermore, the role of radiotherapy in subgroups of patients with unfavorable baseline characteristics (e.g., tumors with comutations like TP53) should be explored as PFS under TKI is shortened compared with TP53 wildtype tumors. 165,166 As clinicians consider the use of radiotherapy combined with TKI, the risk of radiation necrosis needs to be considered.…”

Section: Systemic Treatment Of Nsclc Brain Metastasesmentioning

confidence: 99%

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

Alvarez‐Breckenridge

Remón

Piña

et al. 2022

American Society of Clinical Oncology Educational Book

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The diagnosis of brain metastases has historically been a dreaded, end-stage complication of systemic disease. Additionally, with the increasing effectiveness of systemic therapies that prolong life expectancy and improved imaging tools, the incidence of intracranial progression is becoming more common. Within this context, there has been increasing attention directed at understanding the molecular underpinnings of intracranial progression. Exploring the unique features of brain metastases compared with their extracranial counterparts to identify aberrant signaling pathways, which can be targeted pharmacologically, may help lead to new treatments for this patient population. Additionally, critical discoveries outside the sphere of the central nervous system are increasingly being applied to brain metastases with the emergence of immune checkpoint inhibition, becoming a prevalent treatment option for patients with brain metastases across multiple histologies. As novel treatment strategies are considered, they require thoughtful incorporation of agents that can cross the blood-brain barrier and can synergize with pre-existing agents through rational combinations. Lastly, as clinicians and scientists continue to understand key molecular features of these tumors, they will continue to influence the treatment algorithms that are developing for the management of these patients. Due to the complexity of treatment decisions for patients with brain metastases, an emerging tool is the utilization of multidisciplinary brain metastasis tumor boards to ensure optimal treatment decisions are made and that patients are provided access to applicable clinical trials. Looking to the future, the collective effort to understand the various tumor-intrinsic and tumor-extrinsic factors that promote central nervous system seeding and propagation will have the potential to change the clinical trajectory for these patients.

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“…Another solution is the combined administration of SRS and targeted treatments. Data from retrospective series in oncogene-addicted NSCLC, preliminarily showed promising results in favor of the synergistic effect of this regimen in improving the intracranial disease control ( 66 , 67 ) and this approach is under investigation in ongoing RCTs.…”

Section: Oligometastases (2-4 Lesions)mentioning

confidence: 99%

“…In patients with oligorecurrent or oligoprogressive NSCLC presenting metachronous BMs, the focal approach with SRS is even helpful to delay the start of a systemic treatment or the switch to a new regimen ( 66 ).…”

Section: Oligometastases (2-4 Lesions)mentioning

confidence: 99%

Modern Radiation Therapy for the Management of Brain Metastases From Non-Small Cell Lung Cancer: Current Approaches and Future Directions

et al. 2021

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Brain metastases (BMs) represent the most frequent event during the course of Non-Small Cell Lung Cancer (NSCLC) disease. Recent advancements in the diagnostic and therapeutic procedures result in increased incidence and earlier diagnosis of BMs, with an emerging need to optimize the prognosis of these patients through the adoption of tailored treatment solutions. Nowadays a personalized and multidisciplinary approach should rely on several clinical and molecular factors like patient’s performance status, extent and location of brain involvement, extracranial disease control and the presence of any “druggable” molecular target. Radiation therapy (RT), in all its focal (radiosurgery and fractionated stereotactic radiotherapy) or extended (whole brain radiotherapy) declinations, is a cornerstone of BMs management, either alone or combined with surgery and systemic therapies. Our review aims to provide an overview of the many modern RT solutions available for the treatment of BMs from NSCLC in the different clinical scenarios (single lesion, oligo and poly-metastasis, leptomeningeal carcinomatosis). This includes a detailed review of the current standard of care in each setting, with a presentation of the literature data and of the possible technical solutions to offer a “state-of-art” treatment to these patients. In addition to the validated treatment options, we will also discuss the future perspectives on emerging RT technical strategies (e.g., hippocampal avoidance whole brain RT, simultaneous integrated boost, radiosurgery for multiple lesions), and present the innovative and promising findings regarding the combination of novel targeted agents such as tyrosine kinase inhibitors and immune checkpoint inhibitors with brain irradiation.

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Clinical Value of Upfront Cranial Radiation Therapy in Osimertinib-Treated Epidermal Growth Factor Receptor–Mutant Non-Small Cell Lung Cancer With Brain Metastases

Cited by 25 publications

References 37 publications

Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Intracranial efficacy of alectinib in ALK-positive NSCLC patients with CNS metastases—a multicenter retrospective study

Emerging Systemic Treatment Perspectives on Brain Metastases: Moving Toward a Better Outlook for Patients

Modern Radiation Therapy for the Management of Brain Metastases From Non-Small Cell Lung Cancer: Current Approaches and Future Directions

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