Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

Takaaki Nakashima; Takeshi Nonoshita; Hidenari Hirata; Kouji Inoue; Akira Nagashima; Tadamasa Yoshitake; Kaori Asai; Yoshiyuki Shioyama

doi:10.21873/invivo.11767

Adverse Events of Concurrent Radiotherapy and ALK Inhibitors for Brain Metastases of ALK-Rearranged Lung Adenocarcinoma

In Vivo. 2020 Jan-Feb;34(1):247-253. doi: 10.21873/invivo.11767.

Authors

Takaaki Nakashima^{1

2}, Takeshi Nonoshita², Hidenari Hirata³, Kouji Inoue⁴, Akira Nagashima⁵, Tadamasa Yoshitake³, Kaori Asai³, Yoshiyuki Shioyama³

Affiliations

¹ Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan takaaki813@hotmail.co.jp.
² Department of Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
³ Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
⁴ Department of Respiratory Medicine, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.
⁵ Department of Thoracic Surgery, Kitakyushu Municipal Medical Center, Kitakyushu, Japan.

Abstract

Background: We investigated acute adverse events in patients with brain metastases (BMs) of anaplastic lymphoma kinase-rearranged (ALKr) non-small cell lung cancer (NSCLC) treated with both cranial radiotherapy and tyrosine kinase inhibitors (TKIs) of ALK.

Patients and methods: Acute AEs were retrospectively investigated in patients with BMs of ALKr-NSCLC who received both whole-brain radiotherapy (WBRT) and ALK-TKI. For comparison, they were also assessed in patients with epidermal growth factor receptor (EGFR)-mutated NSCLC and wild-type with neither ALK rearrangement nor EGFR mutation treated with WBRT.

Results: Two ALKr cases were consequently eligible. Grade 3 otitis media unexpectedly occurred in both cases, while there was one case out of 11 and one case out of 18 of grade 2 otitis media among the EGFR-mutated cases and wild-type cases (p=0.013), respectively.

Conclusion: Concurrent treatment with WBRT and ALK-TKI may be associated with acute severe ear toxicity in patients with BMs of ALKr-NSCLC.

Keywords: ALK-TKI; adverse events; brain metastases; lung adenocarcinoma; radiotherapy.

MeSH terms

Adenocarcinoma of Lung / genetics
Adenocarcinoma of Lung / pathology
Adenocarcinoma of Lung / therapy*
Adult
Aged
Anaplastic Lymphoma Kinase / antagonists & inhibitors*
Anaplastic Lymphoma Kinase / genetics*
Antineoplastic Agents / adverse effects
Biomarkers, Tumor
Brain Neoplasms / genetics
Brain Neoplasms / secondary
Brain Neoplasms / therapy*
Carcinoma, Non-Small-Cell Lung / genetics
Carcinoma, Non-Small-Cell Lung / pathology
Carcinoma, Non-Small-Cell Lung / therapy
Chemoradiotherapy / adverse effects*
Cranial Irradiation / adverse effects
Crizotinib / adverse effects
Drug-Related Side Effects and Adverse Reactions / etiology*
ErbB Receptors / genetics
Female
Follow-Up Studies
Gene Expression Regulation, Neoplastic
Gene Rearrangement*
Humans
Lung Neoplasms / genetics
Lung Neoplasms / pathology
Lung Neoplasms / therapy
Male
Middle Aged
Mutation
Prognosis
Radiodermatitis / etiology*
Retrospective Studies

Substances

Antineoplastic Agents
Biomarkers, Tumor
Crizotinib
ALK protein, human
Anaplastic Lymphoma Kinase
EGFR protein, human
ErbB Receptors