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

Abstract

The aim of this follow-up analysis of the ESPATUE phase 3 trial was to explore the prognostic value of postinduction chemotherapy PETmetrics 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 chemoradiotherapywith a cumulative dose of upto 45Gy (1.5Gyper fraction twice aday), followedby 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.18F-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: Ninetytwo patients who underwent 18F-FDG PET/CT after induction chemotherapy were enrolled. Median posttreatment MTV was 5.9 cm3. Altogether, 85 patients completed the whole chemoradiation with the planned total dose of 60-71 Gy. In univariable proportionalhazards analysis, each of 3 parameters - posttreatment MTV, posttreatment SUVmax, and posttreatment maximum total lesion glycolysis (TLGmax(post)) - was associated with overall survival (P < 0.05). Multivariable survival analysis, including clinical and postinduction PET parameters, found TLGmax(post) (hazard ratio, 1.032 [95% CI, 1.013-1.052] per 100 cm3 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 crossvalidated 2-parameter classifier was TLGmax(post) and total radiation dose. TLGmax(post) was associated with time to distant metastases (P = 0.0018), and posttreatment SUVmax 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 18F-FDG PET/CT is a promising diagnostic modality for guiding individualized treatment intensification. COPYRIGHT