ORIGINAL RESEARCH article
Front. Oncol.
Sec. Cancer Imaging and Image-directed Interventions
This article is part of the Research TopicOptimizing Precision Radiotherapy for Locally Advanced Non-Small Cell Lung Cancer: recent advances and innovationsView all 3 articles
Early prediction of tumor response to carbon ion radiotherapy via 18F-FMISO PET/CT in patients with locally advanced non-small-cell lung cancer
Provisionally accepted
- 1Department of Nuclear Medicine, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China
- 2Department of Radiotherapy, Shanghai Proton and Heavy Ion Center, Fudan University Cancer Hospital, Shanghai, China
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Background: Hypoxia increases resistance to carbon ion radiotherapy (CIRT) in locally advanced non-small-cell lung cancer (LA-NSCLC, stage II-III). This study aimed to develop a hypoxia-related model based on 18F-fluoromisonidazole (FMISO) positron emission tomography/computed tomography (PET/CT) for the early prediction of tumor response to CIRT in LA-NSCLC patients, thereby identifying patients most likely to benefit from CIRT. Methods: A total of 42 LA-NSCLC patients, including 25 (60%) with squamous cell carcinoma (SCC) and 17 (40%) with non-SCC, underwent 18F-FMISO PET/CT prior to CIRT. 18F-FMISO maximum standardized uptake values (SUVmax), the tumor-to-muscle ratios (TMR), and hypoxic tumor volume (HTV) were measured, with the TMR ≥ 1.4 threshold defined for hypoxia. The study endpoint was tumor response to CIRT at 3 months. After identifying 18F-FMISO biomarkers related to CIRT response, a prediction model was developed and evaluated using the area under curve (AUC) (95 % confidence interval [CI]). Results: Among the 42 patients analyzed, 17 (40%) achieved partial response (PR) while 25 (60%) had stable disease (SD). 18F-FMISO-PET detected obvious uptake in 31 (74%) patients with LA-NSCLC, although these values were not related to CIRT response (p > 0.05). Subgroup analysis showed that favorable responses were significantly more prevalent in hypoxic SCC (TMR ≥ 1.4, n = 15, 36%) patients with smaller HTV (p < 0.01), whereas 18F-FMISO uptake was not significantly correlated with CIRT response in normoxic SCC (TMR < 1.4, n = 10, 24%) or all non-SCC (n = 17, 40%) patients (all p > 0.05). A positive correlation between tumor size and hypoxia was observed in SCC patients (p < 0.01). Multivariate logistic regression analysis showed that HTV was an independent predictor of CIRT response (p = 0.04, odds ratio = 1.14) with an AUC (95% CI) of 0.89 (0.71-1.00) in hypoxic SCC patients. Conclusion: 18F-FMISO PET/CT is recommended for SCC patients, especially who are likely to have hypoxia predicted by tumor size, and it holds great promise for selecting patients who will benefit from CIRT.
Keywords: 18F-FMISO PET/CT, Locally advanced non-small-cell lung cancer, Carbon ion radiotherapy, Response prediction, tumor hypoxia
Received: 27 Oct 2025; Accepted: 01 Dec 2025.
Copyright: © 2025 Ren, Chen, Mao, Zhang, Li, Wu and Cheng. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jingyi Cheng
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