Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation

Ou, Sai‐Hong Ignatius; Weitz, Michael; Jalas, John R.; Kelly, Daniel F.; Wong, Vanessa; Azada, Michele C.; Quines, Oliver; Klempner, Samuel J.

doi:10.1016/j.lungcan.2016.03.008

Cited by 20 publications

(12 citation statements)

References 11 publications

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“…Alectinib could induce a meaningful response in these patients while allowing prompt initiation of systemic therapy and postponement (or elimination) of the need for brain radiation, with potential sparing from the associated short-and longterm neurotoxicities. [11][12][13][14] For these patients, careful multidisciplinary evaluation at the initial presentation involving the surgical, radiation oncology, and medical oncology teams will be critical, with close clinical followup upon the start of alectinib therapy and early assessment of radiologic response if warranted. Of note, this study did not compare outcomes in patients treated with alectinib first with those in patients treated with CNS RT followed by alectinib.…”

Section: Discussionmentioning

confidence: 99%

“…At present, the standard therapy for symptomatic or large brain lesions remains surgical resection, stereotactic radiosurgery (SRS), whole brain radiotherapy (RT), or some combination thereof, which may delay the initiation of systemic therapy and cause short-and long-term neurotoxicities, including radionecrosis and cognitive impairment. [11][12][13][14] Herein, we report the CNS efficacy of alectinib in ALK-positive NSCLC, focusing on patients with baseline CNS metastases that were symptomatic or at least 1 cm in size.…”

Section: Introductionmentioning

confidence: 99%

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Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Lin

Jiang

Joshipura

et al. 2019

Journal of Thoracic Oncology

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Background: Central nervous system (CNS) metastases represent a significant source of morbidity and mortality for patients with ALK tyrosine kinase gene (ALK)-positive NSCLC. Alectinib has demonstrated robust CNS activity in both crizotinib-naive and crizotinib-resistant settings. However, the CNS efficacy of alectinib has not been established in patients with untreated symptomatic, large CNS metastases. Methods: In this retrospective study, patients were eligible if they had advanced ALK-positive NSCLC with large (defined as 1 cm) or symptomatic CNS metastases and received alectinib. Medical records and radiographic imaging were reviewed to determine treatment outcomes. CNS efficacy was assessed per the modified Response Evaluation Criteria in Solid Tumors version 1.1. Results: Of the 19 patients, 15 (79%) had measurable CNS disease at baseline and were evaluable for response. The CNS objective response rate in these patients was 73.3% (95% confidence interval [CI]: 44.9%-92.2%), the CNS disease control rate was 100.0% (95% CI: 78.2%-100.0%), and the median CNS duration of response was 19.3 months (95% CI: 14.3 months-not evaluable). In 18 evaluable patients with measurable and/or nonmeasurable baseline CNS disease, the CNS objective response rate was 72.2% (95% CI: 46.5%-90.3%), the CNS disease control rate was 100.0% (95% CI: 81.5%-100.0%), and the median CNS duration of response was 17.1 months (95% CI: 14.3 months-not evaluable). All eight patients with symptoms attributable to CNS metastases had clinical improvement upon starting alectinib therapy. Six patients (32%) eventually required salvage brain radiotherapy. Conclusions: Alectinib demonstrated meaningful CNS efficacy in patients with ALK-positive NSCLC with untreated symptomatic or large brain metastases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Lin

Jiang

Joshipura

et al. 2019

Journal of Thoracic Oncology

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“…Given the dramatic response to alectinib, the question was raised whether to pursue stereotactic radiation to the remaining brain lesions. Evidence on this topic is limited, although case reports have shown an increased risk of radionecrosis with alectinib . Therefore, we recommended expectant management with close surveillance.…”

Section: Resultsmentioning

confidence: 99%

A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases

et al. 2017

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A challenge in precision medicine is the identification of actionable driver mutations. Alterations can be identified within the tumor tissue, by small biopsy or fine‐needle aspirates, or by noninvasive methods, such as circulating tumor cells or circulating tumor DNA. This article presents a case of atypical neuroendocrine tumor metastatic to the bone and brain for which circulating tumor DNA analysis found an ALK translocation.

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“…5 We have previously reported that radiation necrosis necessitating neurosurgical resection could occur with alectinib. 8,9 In one case, radiation necrosis occurred after 7 years from the last radiation treatment and 12 months into alectinib treatment. 9 While radiation necrosis did not occur during alectinib treatment in our case 1 patient, symptomatic radiation necrosis occurred twice both requiring neurosurgical resection during lorlatinib treatment with the second episode of radiation necrosis occurring after 11 months into lorlatinib treatment.…”

Section: Discussionmentioning

confidence: 99%

<p>Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases</p>

Zhu¹,

Nagasaka²,

Kubota³

et al. 2020

LCTT

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Central nervous system (CNS) metastasis carries a significant morbidity and mortality in anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC). Next-generation ALK tyrosine kinase inhibitors (TKIs) are highly CNS-penetrant and have demonstrated remarkable intracranial activity across clinical studies, and yet radiation remains the mainstay of treatment modality against CNS metastasis. We have previously reported alectinib can induce CNS radiation necrosis even after a remote history of radiation (7 years post-radiation). Lorlatinib is another potent next-generation ALK TKI that can overcome many ALK resistance mutations and has been shown to have excellent activity in patients with baseline CNS metastasis. Here we report two ALK-rearranged NSCLC patients who developed radiation necrosis shortly after initiating lorlatinib following progression on the sequential treatment of crizotinib, alectinib, and brigatinib. In both cases, radiation necrosis is evidenced by serial MRI images and histological examination of the resected CNS metastasis that had previously been radiated. Our cases highlight the importance of recognizing CNS radiation necrosis that may mimic disease progression in ALK-rearranged NSCLC treated with and potentially precipated by next-generation ALK TKIs.

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Alectinib induced CNS radiation necrosis in an ALK+NSCLC patient with a remote (7 years) history of brain radiation

Cited by 20 publications

References 11 publications

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

Efficacy of Alectinib in Patients with ALK-Positive NSCLC and Symptomatic or Large CNS Metastases

A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases

<p>Symptomatic CNS Radiation Necrosis Requiring Neurosurgical Resection During Treatment with Lorlatinib in ALK-Rearranged NSCLC: A Report of Two Cases</p>

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