European journal of nuclear medicine and molecular imaging · 2026
Improved early response assessment of chemoimmunotherapy efficacy by 68Ga-grazytracer PET/CT in non-small cell lung cancer: a comparison of bronchial arterial versus intravenous chemotherapy.
СтатьяСравнительное исследованиеПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Shen Xiuling, Wang Zhengjie, Xia Zhu, Yi Yupin, Li Wenbo, Zhang Rui, Zhang Xiaoyang, Xia Biao, Jiang Weibin, Zheng Chunxiao, Wang Qin, Li Jia, Li Jianqiu, Xu Lu, Liu Zhaofei, Li Nan, Pang Hua
Аннотация
BACKGROUND: Chemoimmunotherapy outperforms immunotherapy alone in advanced non-small cell lung cancer (NSCLC). However, current anatomical imaging and programmed death-ligand 1 (PD-L1) assessments are insufficient for early response prediction and do not directly capture treatment-induced immune effector function. Whether 68Ga-grazytracer PET/CT, which visualizes granzyme B as a marker of CD8+ T‑cell effector function, could assess early response and reveal potential differences between intravenous and bronchial arterial infusion (BAI)-based chemoimmunotherapy remains unknown.
METHODS: In this prospective study, 60 patients with advanced NSCLC receiving BAI-based (n = 28) or intravenous (n = 32) chemoimmunotherapy underwent 68Ga-grazytracer PET/CT after 1-2 treatment cycles. The primary endpoint was a 6-month objective response (iRECIST). Secondary endpoints compared immune activation between groups and the performance of 68Ga-grazytracer PET/CT for early response assessment versus conventional biomarkers (baseline tumor size [SLD], early anatomical change [ΔSLD], and PD-L1 expression). Statistical analyses included ROC curve analysis, logistic regression, and bootstrap internal validation.
RESULTS: BAI-based chemoimmunotherapy showed higher 68Ga-grazytracer uptake (maximum standardized uptake value [SUVmax]: 2.86 ± 0.71 vs. 2.19 ± 0.80, P = 0.001) and objective response rate (60.71% vs. 34.38%, P = 0.04) than intravenous chemoimmunotherapy, suggesting a possible association with enhanced immune activation. The SUVmax demonstrated strong discriminative value for objective response (overall apparent AUC = 0.90; optimism-corrected = 0.89) and was the only independent early-response indicator, outperforming anatomical response metrics (SLD: AUC = 0.57; ΔSLD: AUC = 0.63) and PD-L1 expression (AUC = 0.45). The discriminative accuracy of the SUVmax was higher in the BAI cohort (apparent AUC = 0.99; corrected = 0.97) than in the intravenous cohort (apparent AUC = 0.83; corrected = 0.83). The corroborative performance of the tumor-to-blood ratio was not significantly different from that of SUVmax.
CONCLUSIONS: 68Ga-grazytracer PET/CT is a promising early imaging biomarker for the response to chemoimmunotherapy in advanced NSCLC patients, particularly those receiving BAI-based regimens. Larger validation studies with uniform protocols are needed to validate these findings and assess its clinical utility.
TRIAL REGISTRATION: ChiCTR2500105792, the registration date is 2025-07-10, https://www.chictr.org.cn/showproj.html?proj=275165 .
METHODS: In this prospective study, 60 patients with advanced NSCLC receiving BAI-based (n = 28) or intravenous (n = 32) chemoimmunotherapy underwent 68Ga-grazytracer PET/CT after 1-2 treatment cycles. The primary endpoint was a 6-month objective response (iRECIST). Secondary endpoints compared immune activation between groups and the performance of 68Ga-grazytracer PET/CT for early response assessment versus conventional biomarkers (baseline tumor size [SLD], early anatomical change [ΔSLD], and PD-L1 expression). Statistical analyses included ROC curve analysis, logistic regression, and bootstrap internal validation.
RESULTS: BAI-based chemoimmunotherapy showed higher 68Ga-grazytracer uptake (maximum standardized uptake value [SUVmax]: 2.86 ± 0.71 vs. 2.19 ± 0.80, P = 0.001) and objective response rate (60.71% vs. 34.38%, P = 0.04) than intravenous chemoimmunotherapy, suggesting a possible association with enhanced immune activation. The SUVmax demonstrated strong discriminative value for objective response (overall apparent AUC = 0.90; optimism-corrected = 0.89) and was the only independent early-response indicator, outperforming anatomical response metrics (SLD: AUC = 0.57; ΔSLD: AUC = 0.63) and PD-L1 expression (AUC = 0.45). The discriminative accuracy of the SUVmax was higher in the BAI cohort (apparent AUC = 0.99; corrected = 0.97) than in the intravenous cohort (apparent AUC = 0.83; corrected = 0.83). The corroborative performance of the tumor-to-blood ratio was not significantly different from that of SUVmax.
CONCLUSIONS: 68Ga-grazytracer PET/CT is a promising early imaging biomarker for the response to chemoimmunotherapy in advanced NSCLC patients, particularly those receiving BAI-based regimens. Larger validation studies with uniform protocols are needed to validate these findings and assess its clinical utility.
TRIAL REGISTRATION: ChiCTR2500105792, the registration date is 2025-07-10, https://www.chictr.org.cn/showproj.html?proj=275165 .