Treatment options for patients with brain metastases from EGFR / ALK -driven lung cancer

Doherty, Mark; Korpanty, Grzegorz; Tomasini, Pascale; Alizadeh, M.; Jao, Kevin; Labbé, Catherine; Mascaux, Céline; Martin, Petra; Kamel‐Reid, Suzanne; Tsao, Ming‐Sound; Pintilie, Melania; Liu, Geoffrey; Bradbury, Penelope Ann; Feld, Ronald; Leighl, Natasha B.; Chung, Caroline; Shepherd, Frances A.

doi:10.1016/j.radonc.2017.03.007

Cited by 44 publications

(40 citation statements)

References 37 publications

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“…Several phase III trials were conducted but no firm conclusion applicable for the entire patient population could be drawn 18,19 . The prediction of the risk of BM development and indication for WBRT to prevent brain dissemination is particularly interesting for specific populations such as EGFR or ALK positive NSCLC patients, for whose incidence of BMs is high [20][21][22] . This points to the need of rational tools to decide therapeutic action in a patient-specific way.…”

Section: Several Biological and Clinical Open Questions Can Be Formulmentioning

confidence: 99%

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer

Bilous

Serdjebi

Boyer

et al. 2018

Preprint

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Brain metastases (BMs) are associated with poor prognosis in non-small cell lung cancer (NSCLC), but are only visible when large enough. Therapeutic decisions such as whole brain radiation therapy would benefit from patientspecific predictions of radiologically undetectable BMs. Here, we propose a mathematical modeling approach and use it to analyze clinical data of BM from NSCLC.Primary tumor growth was best described by a gompertzian model for the prediagnosis history, followed by a tumor growth inhibition model during treatment.Growth parameters were estimated only from the size at diagnosis and histology, but predicted plausible individual estimates of the tumor age (2.1-5.3 years). Multiple metastatic models were assessed from fitting either literature data of BM probability (n = 183 patients) or longitudinal measurements of visible BMs in two patients. Among the tested models, the one featuring dormancy was best able to describe the data. It predicted latency phases of 4.4 -5.7 months and onset of BMs 14 -19 months before diagnosis. This quantitative model paves the way for a computational tool of potential help during therapeutic management.

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Section: Several Biological and Clinical Open Questions Can Be Formulmentioning

confidence: 99%

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer

Bilous

Serdjebi

Boyer

et al. 2018

Preprint

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“…Patients with metastatic NSCLC who are of good performance status should receive palliative systemic therapy. In patients receiving either palliative chemotherapy or targeted agents, whole brain radiotherapy can be delayed without a detriment to survival . Some may argue that stereotactic radiosurgery (SRS) in addition to whole brain radiotherapy has a survival advantage in patients with solitary metastasis .…”

mentioning

confidence: 99%

“…In patients receiving either palliative chemotherapy or targeted agents, whole brain radiotherapy can be delayed without a detriment to survival. [10][11][12] Some may argue that stereotactic radiosurgery (SRS) in addition to whole brain radiotherapy has a survival advantage in patients with solitary metastasis. 13 RTOG 9508 stated this in the abstract, however, on closer reading the purported survival benefit did not reach statistical significance on multivariate analysis.…”

mentioning

confidence: 99%

Should we screen for brain metastases in non‐small cell lung cancer?

Vinod

2018

J Med Imag Rad Onc

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“…Furthermore, patients with a progression but failing to receive RT were excluded from the present study. In the recent series of Doherty et al including 184 patients, 20 patients had a third line cranial nervous system treatment for progressive disease including even surgery, a complete new paradigm in the patient management with brain metastases (2).…”

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confidence: 99%

“…Looking to the papers published on the topics, results are conflicting with benefit in term of response for combining RT and TKIs, better brain control but no major differences in survival questioning to start or not with RT or keeping it until progression (2)(3)(4)8,9). A meta-analysis by Jiang et al included 15 studies and 1,552 patients: RT plus EGFR TkIs significantly improve the response rate, prolong time to central nervous tumor progression and even median survival at the price of an increase in toxicity (10).…”

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confidence: 99%

Can we omit radiotherapy in case of brain metastases for patients with mutant EGFR lung adenocarcinoma?

Houtte

Devriendt

2017

Transl. Lung Cancer Res.

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The paper presented by Magnuson et al. is a multiinstitutional retrospective study looking to the treatment of brain metastases among patients with tyrosine kinase inhibitor naive epidermal growth factor mutant non-small cell lung cancer: they concluded that deferral of radiotherapy is associated with inferior survival and the best approach is radiosurgery (RS) followed by EGFR-TKI to avoid the neurocognitive toxicity of whole brain radiotherapy (WBRT) (1). This is currently a hot question in the literature with those favoring a combined approach and those favoring only TKI. This is certainly not an easy question as there are many possible endpoints to evaluate the efficacy of the treatment: local response, time to brain progression, quality of life, toxicity and overall survival, the ultimate endpoint. The later will directly be influenced not only by the brain tumor control but also by the extracranial metastatic disease and the response to the systemic treatment which may explain the differences reported in the literature. We also must point out the fact that all studies are retrospective with all the possible biases due to this approach: the choice of treatment is often related to the practitioner both for radiotherapy and the type of treatment (WBRT or RS) and the treatment timing. In a recent paper, Doherty et al. has observed a longer time to intracranial progression (TTIP) with WBRT compared to RS or TKI but no difference in survival suggesting that WBRT may be deferred until cranial progression: nevertheless, the rate of patients with brain symptomatic lesions was higher in the WBRT group, 52% vs. 16% for RS and 11% for the TKI (2). A similar observation in Byeon series was in favor of only TKI (3). Other series may include only asymptomatic patients such as in Liu's paper (4).A first comment is certainly the changing pattern of outcome for this group of patients: median overall survival for the three cohorts of patients range from 25 months for the TKI only group to 30 and 46 months for the combined approach with WBRT or RS. This is major improvement in contrast to the results observed in the study of Gaspar et al. with patients included in three randomized trials of the RTOG: using the recursive partitioning analysis (RPA) including four variables (age, performance status, control of primary disease and extracranial metastases); a median survival time of 7.7 months was observed for the best group and less than 3 months for the worse (5). In our experience with the Leksell Gamma Knife RS and using the basic score for brain metastases which includes the performance status, the presence or absence of extracranial disease, the control or not of the primary disease, the median survival rose from 2.4 months for the worse subgroup to more than 30 months for the best subgroup (6).This major improvement in patient's survival is partially related to the patient selection but also outline the efficacy of the current systemic treatment, especially the targeted agents in a population with EGFR mutant adenocarcinoma...

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Treatment options for patients with brain metastases from EGFR / ALK -driven lung cancer

Cited by 44 publications

References 37 publications

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer

Quantitative mathematical modeling of clinical brain metastasis dynamics in non-small cell lung cancer

Should we screen for brain metastases in non‐small cell lung cancer?

Can we omit radiotherapy in case of brain metastases for patients with mutant EGFR lung adenocarcinoma?

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