Optimal timing and clinical value of radiotherapy in advanced ALK-rearranged non-small cell lung cancer with or without baseline brain metastases: ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-03-13

AUTHORS

Jianjiao Ni, Guodong Li, Xi Yang, Li Chu, Jialei Wang, Yida Li, Liqing Zou, Yuan Li, Congying Xie, Zhengfei Zhu

ABSTRACT

BackgroundDespite development of several next-generation tyrosine kinase inhibitors (TKIs), crizotinib remains one of the first-line treatment options for advanced ALK-positive NSCLC and is widely used in situations where next-generation TKIs aren’t yet approved or economically inaccessible. However, the pattern of failure and clinical value of radiotherapy in metastatic crizotinib-treated ALK-mutant lung cancer, with or without baseline brain metastases (BBM), are largely unknown.MethodsConsecutive crizotinib-treated NSCLC patients with adequate imaging and measurable disease were retrospectively enrolled. Disease progression in original sites (primary/metastatic), new sites, or both, are classified as original failure (OF), distant failure (DF) and ODF, respectively. Progression free survival, from crizotinib initiation to the first disease progression, and from that to the second disease progression, were calculated as PFS1 and PFS2.ResultsNinety-three patients were identified. With a median follow up of 22.0 (range, 2.0–72.0) months, 52 patients had crizotinib-treatment failure. The frequencies of OF, ODF, and DF, were 50.0, 26.9, and 23.1%, respectively. Histology, primary tumor size and presence of BBM, were independently associated with OF, using competing risks analyses. The brain was the most common site of initial disease progression. Patients with BBM had a significant higher possibility developing multiple-progressive lesions in the brain (p = 0.002). Importantly, four of the ten patients who had baseline oligo-metastatic cranial disease but didn’t receive upfront brain radiation, developed multiple-progressive disease in the brain. Brain radiation before crizotinib could alter the disease failure patterns and improve PFS1 among patients with BBM (p = 0.006). Extracranial radiation was efficient in controlling symptoms but it was not associated with PFS1 (p = 0.223), and the majority of patients were eligible for salvage radiotherapy upon disease progression to crizotinib. By the time of data cut-off, 28 patients had second disease progression, with a median PFS2 of 7.0 (95% CI 5.4–8.6) months and salvage radiotherapy significantly prolonged PFS2 (p = 0.003). Additionally, patients receiving any radiotherapy during their treatment course had a significant longer overall survival (p = 0.048).ConclusionsAmong patients with baseline oligo-metastatic brain lesions which are suitable for stereotactic radiosurgery, upfront brain radiotherapy provides considerable clinical benefits. While, extracranial radiation may be deferred in asymptomatic patients with multiple-metastatic lesions. More... »

PAGES

44

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s13014-019-1240-1

DOI

http://dx.doi.org/10.1186/s13014-019-1240-1

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112739159

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30866974


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26 schema:description BackgroundDespite development of several next-generation tyrosine kinase inhibitors (TKIs), crizotinib remains one of the first-line treatment options for advanced ALK-positive NSCLC and is widely used in situations where next-generation TKIs aren’t yet approved or economically inaccessible. However, the pattern of failure and clinical value of radiotherapy in metastatic crizotinib-treated ALK-mutant lung cancer, with or without baseline brain metastases (BBM), are largely unknown.MethodsConsecutive crizotinib-treated NSCLC patients with adequate imaging and measurable disease were retrospectively enrolled. Disease progression in original sites (primary/metastatic), new sites, or both, are classified as original failure (OF), distant failure (DF) and ODF, respectively. Progression free survival, from crizotinib initiation to the first disease progression, and from that to the second disease progression, were calculated as PFS1 and PFS2.ResultsNinety-three patients were identified. With a median follow up of 22.0 (range, 2.0–72.0) months, 52 patients had crizotinib-treatment failure. The frequencies of OF, ODF, and DF, were 50.0, 26.9, and 23.1%, respectively. Histology, primary tumor size and presence of BBM, were independently associated with OF, using competing risks analyses. The brain was the most common site of initial disease progression. Patients with BBM had a significant higher possibility developing multiple-progressive lesions in the brain (p = 0.002). Importantly, four of the ten patients who had baseline oligo-metastatic cranial disease but didn’t receive upfront brain radiation, developed multiple-progressive disease in the brain. Brain radiation before crizotinib could alter the disease failure patterns and improve PFS1 among patients with BBM (p = 0.006). Extracranial radiation was efficient in controlling symptoms but it was not associated with PFS1 (p = 0.223), and the majority of patients were eligible for salvage radiotherapy upon disease progression to crizotinib. By the time of data cut-off, 28 patients had second disease progression, with a median PFS2 of 7.0 (95% CI 5.4–8.6) months and salvage radiotherapy significantly prolonged PFS2 (p = 0.003). Additionally, patients receiving any radiotherapy during their treatment course had a significant longer overall survival (p = 0.048).ConclusionsAmong patients with baseline oligo-metastatic brain lesions which are suitable for stereotactic radiosurgery, upfront brain radiotherapy provides considerable clinical benefits. While, extracranial radiation may be deferred in asymptomatic patients with multiple-metastatic lesions.
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33 schema:keywords ALK
34 ALK-mutant lung cancer
35 ALK-positive NSCLC
36 BackgroundDespite development
37 ConclusionsAmong patients
38 MethodsConsecutive crizotinib
39 NSCLC
40 NSCLC patients
41 ODF
42 PFS1
43 PFS2
44 adequate imaging
45 advanced ALK
46 advanced ALK-positive NSCLC
47 analysis
48 asymptomatic patients
49 baseline brain metastases
50 baseline oligo-metastatic brain lesions
51 baseline oligo-metastatic cranial disease
52 benefits
53 brain
54 brain lesions
55 brain metastases
56 brain radiation
57 brain radiotherapy
58 cancer
59 cell lung cancer
60 clinical benefit
61 clinical value
62 common site
63 considerable clinical benefit
64 course
65 cranial disease
66 crizotinib
67 crizotinib initiation
68 crizotinib-treated ALK-mutant lung cancer
69 crizotinib-treatment failure
70 cut
71 data cut
72 development
73 disease
74 disease failure patterns
75 disease progression
76 distant failure
77 extracranial radiation
78 failure
79 failure analysis
80 failure patterns
81 first disease progression
82 first-line treatment option
83 follow
84 free survival
85 frequency
86 high possibility
87 histology
88 imaging
89 implications
90 inhibitors
91 initial disease progression
92 initiation
93 kinase inhibitors
94 lesions
95 longer overall survival
96 lung cancer
97 majority
98 majority of patients
99 measurable disease
100 median PFS2
101 median follow
102 metastasis
103 metastatic crizotinib-treated ALK-mutant lung cancer
104 months
105 multiple-metastatic lesions
106 multiple-progressive disease
107 multiple-progressive lesions
108 new sites
109 next-generation tyrosine kinase inhibitors
110 non-small cell lung cancer
111 oligo-metastatic brain lesions
112 oligo-metastatic cranial disease
113 optimal timing
114 options
115 original failure
116 original site
117 overall survival
118 patients
119 patterns
120 patterns of failure
121 possibility
122 presence
123 presence of BBM
124 primary tumor size
125 progression
126 radiation
127 radiosurgery
128 radiotherapy
129 risk analysis
130 salvage radiotherapy
131 second disease progression
132 significant higher possibility
133 significant longer overall survival
134 sites
135 situation
136 size
137 stereotactic radiosurgery
138 survival
139 symptoms
140 time
141 timing
142 treatment course
143 treatment options
144 tumor size
145 tyrosine kinase inhibitors
146 upfront brain radiation
147 upfront brain radiotherapy
148 values
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