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

The aim of this follow-up analysis of the ESPATUE phase 3 trial was to explore the prognostic value of postinduction chemotherapy PET metrics in patients with stage III non–small cell lung cancer who were assigned to receive definitive chemoradiotherapy. Methods: All eligible stage IIIA (cN2) and stage IIIB patients in the trial received an induction doublet chemotherapy consisting of 3 cycles with cisplatin and paclitaxel, and subsequent combined chemoradiotherapy with a cumulative dose of up to 45 Gy (1.5 Gy per fraction twice a day), followed by a radiation boost (2 Gy once per day) with concurrent continuation of doublet chemotherapy with cisplatin and vinorelbine. The protocol definition prescribed a total dose of 65–71 Gy. (18)F-FDG PET/CT was performed at study entry and before concurrent chemoradiotherapy. Interim PET 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 (18)F-FDG PET/CT after induction chemotherapy were enrolled. Median posttreatment MTV was 5.9 cm(3). Altogether, 85 patients completed the whole chemoradiation with the planned total dose of 60–71 Gy. In univariable proportional-hazards analysis, each of 3 parameters—posttreatment MTV, posttreatment SUV(max), and posttreatment maximum total lesion glycolysis (TLG(max(post)))—was associated with overall survival (P < 0.05). Multivariable survival analysis, including clinical and postinduction PET parameters, found TLG(max(post)) (hazard ratio, 1.032 [95% CI, 1.013–1.052] per 100 cm(3) increase) and total radiation dose (hazard ratio, 0.930 [95% CI, 0.902–0.959] per 1 Gy increase) was significantly related to overall survival in the whole group of patients and in patients receiving a total dose of at least 60 Gy. The best leave-one-out cross-validated 2-parameter classifier was TLG(max(post)) and total radiation dose. TLG(max(post)) was associated with time to distant metastases (P = 0.0018), and posttreatment SUV(max) was associated with time to locoregional relapse (P = 0.039), in multivariable analysis of patients receiving a total dose of at least 60 Gy. Conclusion: Postinduction chemotherapy PET parameters demonstrated prognostic significance. Therefore, interim (18)F-FDG PET/CT is a promising diagnostic modality for guiding individualized treatment intensification.