Background This study aimed to assess the predictive and evaluative value of PD-L1 targeted 68Ga-THP-APN09 PET/CT in the neoadjuvant immunotherapy combined with chemotherapy for resectable non-small cell lung cancer (NSCLC), and to explore its potential in indicating immunotherapy-related adverse effects (irAEs). Methods Fifty patients with resectable NSCLC enrolled in this prospective study underwent baseline 68Ga-THP-APN09 PET/CT and 18F-FDG PET/CT, with follow-up 18F-FDG PET/CT conducted, additionally, 36 patients received follow-up 68Ga-THP-APN09 PET/CT. Surgery was performed following 2–4 cycles of toripalimab combined with chemotherapy if R0 resection was feasible. The major pathologic response (MPR) state of the post-operative specimen and the adverse effects following combined therapy were documented. The correlation between PD-L1 expression and baseline 68Ga-THP-APN09 PET/CT uptake was determined. The predictive and evaluative efficacies of baseline and follow-up 68Ga-THP-APN09 PET/CT, along with 18F-FDG PET/CT, in determining MPR, were compared. Results The SUVmax values of baseline 68Ga-THP-APN09 PET/CT were significantly higher in patients exhibiting high-positive PD-L1 expression compared to those with low-positive and negative expression (P = 0.001). And the SUVmax values of baseline 68Ga-THP-APN09 PET/CT in the response group, as determined by 18F-FDG PET/CT evaluation, were significantly higher than those in the non-response group (3.4 vs. 2.4, P < 0.001). Totally, 41 patients underwent surgery, of which 27 achieved MPR, while 14 did not. The SUVmax in baseline 68Ga-THP-APN09 PET/CT demonstrated statistical significance between the MPR and non-MPR groups, with area under the ROC curve (AUC) of 0.88 (95%CI: 0.77–0.99) in identifying MPR. However, the SUVmax in baseline 18F-FDG PET/CT failed to demonstrated significant predictive power, with AUC values of 0.68 (95%CI: 0.50–0.86, P = 0.076). While the SUVmax in follow-up 68Ga-THP-APN09 and 18F-FDG PET/CT, along with their change rate (ΔSUVmax%), demonstrated good predictive efficacy in identifying MPR, with AUC values of 0.81 (0.64–0.98), 0.91 (0.82–1.00), 0.93 (0.84–1.00), and 0.96 (0.89–1.00), respectively. Furthermore, the follow-up 68Ga-THP-APN09 PET/CT could remarkedly indicate the potential for thyroiditis. Conclusion Baseline 68Ga-THP-APN09 PET/CT alone could predict efficacy and assist in patient screening for immunotherapy combined chemotherapy in resectable NSCLC, and the follow-up 68Ga-THP-APN09 PET/CT and their change rates could aid in therapy evaluation. Additionally, follow-up 68Ga-THP-APN09 PET/CT could be utilized to monitor the immunotherapy-related thyroiditis during the therapy. Trial registration NCT05156515, registered 8 December 2021, <a href="https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw">https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw</a>.

Efficacy of radiolabelled PD-L1-targeted nanobody in predicting and evaluating the combined immunotherapy and chemotherapy for resectable non-small cell lung cancer

期刊论文
发表日期：

2025年2月6日

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Xin Zhou,
Shi Yan,
Xiaopan Ma,
Hua Zhu,
Bing Liu,
Xin Yang,
Bing Jia,
Zhi Yang,
Nan Wu,
Nan Li

摘要

Background

This study aimed to assess the predictive and evaluative value of PD-L1 targeted ⁶⁸Ga-THP-APN09 PET/CT in the neoadjuvant immunotherapy combined with chemotherapy for resectable non-small cell lung cancer (NSCLC), and to explore its potential in indicating immunotherapy-related adverse effects (irAEs).

Methods

Fifty patients with resectable NSCLC enrolled in this prospective study underwent baseline ⁶⁸Ga-THP-APN09 PET/CT and ¹⁸F-FDG PET/CT, with follow-up ¹⁸F-FDG PET/CT conducted, additionally, 36 patients received follow-up ⁶⁸Ga-THP-APN09 PET/CT. Surgery was performed following 2–4 cycles of toripalimab combined with chemotherapy if R0 resection was feasible. The major pathologic response (MPR) state of the post-operative specimen and the adverse effects following combined therapy were documented. The correlation between PD-L1 expression and baseline ⁶⁸Ga-THP-APN09 PET/CT uptake was determined. The predictive and evaluative efficacies of baseline and follow-up ⁶⁸Ga-THP-APN09 PET/CT, along with ¹⁸F-FDG PET/CT, in determining MPR, were compared.

Results

The SUV_max values of baseline ⁶⁸Ga-THP-APN09 PET/CT were significantly higher in patients exhibiting high-positive PD-L1 expression compared to those with low-positive and negative expression (P = 0.001). And the SUV_max values of baseline ⁶⁸Ga-THP-APN09 PET/CT in the response group, as determined by ¹⁸F-FDG PET/CT evaluation, were significantly higher than those in the non-response group (3.4 vs. 2.4, P < 0.001). Totally, 41 patients underwent surgery, of which 27 achieved MPR, while 14 did not. The SUV_max in baseline ⁶⁸Ga-THP-APN09 PET/CT demonstrated statistical significance between the MPR and non-MPR groups, with area under the ROC curve (AUC) of 0.88 (95%CI: 0.77–0.99) in identifying MPR. However, the SUV_max in baseline ¹⁸F-FDG PET/CT failed to demonstrated significant predictive power, with AUC values of 0.68 (95%CI: 0.50–0.86, P = 0.076). While the SUV_max in follow-up ⁶⁸Ga-THP-APN09 and ¹⁸F-FDG PET/CT, along with their change rate (ΔSUV_max%), demonstrated good predictive efficacy in identifying MPR, with AUC values of 0.81 (0.64–0.98), 0.91 (0.82–1.00), 0.93 (0.84–1.00), and 0.96 (0.89–1.00), respectively. Furthermore, the follow-up ⁶⁸Ga-THP-APN09 PET/CT could remarkedly indicate the potential for thyroiditis.

Conclusion

Baseline ⁶⁸Ga-THP-APN09 PET/CT alone could predict efficacy and assist in patient screening for immunotherapy combined chemotherapy in resectable NSCLC, and the follow-up ⁶⁸Ga-THP-APN09 PET/CT and their change rates could aid in therapy evaluation. Additionally, follow-up ⁶⁸Ga-THP-APN09 PET/CT could be utilized to monitor the immunotherapy-related thyroiditis during the therapy.

Trial registration

NCT05156515, registered 8 December 2021, https://register.clinicaltrials.gov/prs/app/action/SelectProtocol?sid=S000BMSI%26;selectaction=Edit%26;uid=U000503E%26;ts=2%26;cx=zeghuw.