Patterns of failure in metastatic ALK-positive NSCLC treated with crizotinib: implications for consolidative stereotactic body radiotherapy
- 1Department of Radiation Oncology, Chongqing University Cancer Hospital, Chongqing, China
- 2Chongqing Key Laboratory of Translational Research for Cancer Metastasis and Individualized Treatment, Chongqing University Cancer Hospital, Chongqing, China
Abstract
Background: Acquired resistance limits durable control with crizotinib in metastatic ALK-positive non–small cell lung cancer (NSCLC). We characterized residual disease and initial progression patterns and identified predictors of candidates for consolidative stereotactic body radiation therapy (SBRT).
Methods: Patients with stage IV ALK-rearranged NSCLC treated with crizotinib (2017–2024) were retrospectively reviewed. Response was assessed per RECIST v1.1. Initial progression was classified as original-site failure (OF), new-site failure (NF), or combined OF and NF (ONF). SBRT eligibility at maximal response was determined using NRG-BR001 criteria and predefined cranial stereotactic radiotherapy criteria. Predictors of eligibility were evaluated using penalized selection followed by logistic regression.
Results: Sixty patients were analyzed. Median time to maximal response was 3.5 months; 15 (25.0%) met SBRT eligibility criteria. Progression occurred in 83.3% (median time to progression, 14.1 months), and oligoprogression occurred in 56%. Lung (50%) and brain (35.7%) were the most common progression sites; initial failure occurred as OF in 34%, NF in 40%, and ONF in 26%. Notably, among SBRT-eligible patients, 66.7% progressed—most often in the brain (50%) and lung (33.3%)—with failures skewed toward NF (50%) rather than OF (30%) or ONF (20%). Independent predictors of SBRT eligibility were female sex, N0–2 disease, absence of baseline bone metastases, and involvement of < 2 metastatic organs.
Conclusions: Progression on crizotinib is frequently oligoprogressive and commonly involves intrathoracic disease, with substantial contributions from both baseline-lesion progression and new-site failure. Consolidative SBRT appears feasible in a subset at maximal response. The identified predictors of SBRT eligibility should be considered exploratory and require external validation in larger prospective cohorts.
Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16600-3.
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BibTeX
@article{wang2026patterns,
title = {{Patterns of failure in metastatic ALK-positive NSCLC treated with crizotinib: implications for consolidative stereotactic body radiotherapy}},
author = {Zhili Wang and Zexi Xu and Lulu Wang and Mao Sun and Jueling Tan and Wei Zhou and Yongzhong Wu and Dan Tao},
journal = {BMC Cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16600-3},
url = {https://doi.org/10.1186/s12885-026-16600-3},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - Patterns of failure in metastatic ALK-positive NSCLC treated with crizotinib: implications for consolidative stereotactic body radiotherapy
AU - Zhili Wang
AU - Zexi Xu
AU - Lulu Wang
AU - Mao Sun
AU - Jueling Tan
AU - Wei Zhou
AU - Yongzhong Wu
AU - Dan Tao
PY - 2026
DA - 2026/08/07
JO - BMC Cancer
DO - 10.1186/s12885-026-16600-3
UR - https://doi.org/10.1186/s12885-026-16600-3
AB - Background: Acquired resistance limits durable control with crizotinib in metastatic ALK-positive non–small cell lung cancer (NSCLC). We characterized residual disease and initial progression patterns and identified predictors of candidates for consolidative stereotactic body radiation therapy (SBRT). Methods: Patients with stage IV ALK-rearranged NSCLC treated with crizotinib (2017–2024) were retrospectively reviewed. Response was assessed per RECIST v1.1. Initial progression was classified as original-site failure (OF), new-site failure (NF), or combined OF and NF (ONF). SBRT eligibility at maximal response was determined using NRG-BR001 criteria and predefined cranial stereotactic radiotherapy criteria. Predictors of eligibility were evaluated using penalized selection followed by logistic regression. Results: Sixty patients were analyzed. Median time to maximal response was 3.5 months; 15 (25.0%) met SBRT eligibility criteria. Progression occurred in 83.3% (median time to progression, 14.1 months), and oligoprogression occurred in 56%. Lung (50%) and brain (35.7%) were the most common progression sites; initial failure occurred as OF in 34%, NF in 40%, and ONF in 26%. Notably, among SBRT-eligible patients, 66.7% progressed—most often in the brain (50%) and lung (33.3%)—with failures skewed toward NF (50%) rather than OF (30%) or ONF (20%). Independent predictors of SBRT eligibility were female sex, N0–2 disease, absence of baseline bone metastases, and involvement of < 2 metastatic organs. Conclusions: Progression on crizotinib is frequently oligoprogressive and commonly involves intrathoracic disease, with substantial contributions from both baseline-lesion progression and new-site failure. Consolidative SBRT appears feasible in a subset at maximal response. The identified predictors of SBRT eligibility should be considered exploratory and require external validation in larger prospective cohorts. Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1186/s12885-026-16600-3.
SN - 1471-2407
ER -