Prognostic Value of Postinduction Chemotherapy Volumetric PET/CT Parameters for Stage IIIA or IIIB Non–Small Cell Lung Cancer Patients Receiving Definitive Chemoradiotherapy

Purpose/Objective(s): The aim of this follow-up analysis of the ESPATUE phase-3 trialwas to explore the prognostic value of post-induction chemotherapy PET metrics in patients with stage III non-small cell lung cancer (NSCLC) who were assigned to receive definitive chemoradiotherapy.

Materials/Methods: All eligible patients stage IIIA (cN2) and stage IIIB of the trial received induction chemotherapy consisting of 3 cycles of cisplatin/paclitaxel and chemoradiotherapy up to 45 Gy/1.5 Gy per fraction twice-a-day, followed by a radiation-boost with 2 Gy once per day with concurrent cisplatin/vinorelbine. The protocol definition prescribed a total dose of 65-71 Gy. 18F-FDG-PET/CT (PETpre) was performed at study entry and before concurrent chemoradiotherapy (interim-PET; PETpost). Interim PETpost metrics and known prognostic clinical parameters were correlated in uni- and multivariable survival analyses. Leave-one-out cross-validation was used to show internal validity.

Results: Ninety-two patients who underwent 18F-FDG-PET/CT after induction chemotherapy were enrolled. Median MTVpost value was 5.9 ml. Altogether 85 patients completed the whole chemoradiation with the planned total dose of 60–71 Gy. In univariable proportional hazard analysis, each of the parameters MTVpost, SUVmax(post) and TLGmax(post) was associated with overall survival (p < 0.05). Multivariable survival analysis, including clinical and post-induction PET parameters, found TLGmax(post) (hazard ratio: 1.032 (95%-CI: 1.013–1.052) per 100 ml increase) and total radiation dose (hazard ratio: 0.930 (0.902–0.959) per Gray increase) significantly related with overall survival in the whole group of patients, and also in patients receiving a total dose ≥ 60 Gy. The best leave-one-out cross-validated 2-parameter classifier contained TLGmax(post) and total radiation dose. TLGmax(post) was associated with time to distant metastases (p = 0.0018), and SUVmax(post) with time to loco-regional relapse (p = 0.039) in multivariable analysis of patients receiving a total dose ≥ 60 Gy.

Conclusion: Post-induction chemotherapy PET parameters demonstrated prognostic significance. Therefore, an interim 18F-FDG-PET/CT is a promising diagnostic modality for guiding individualized treatment intensification.


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