PROGNOSTIC VALUE OF POST-INDUCTION CHEMOTHERAPY VOLUMETRIC PET/CT PARAMETERS FOR STAGE IIIA/B NON-SMALL CELL LUNG CANCER PATIENTS RECEIVING DEFINITIVE CHEMORADIOTHERAPY

Maja Guberina; Christoph Poettgen; Martin Metzenmacher; Marcel Wiesweg; Martin Schuler; Clemens Aigner; Till Ploenes; Lale Umutlu; Thomas Gauler; Kaid Darwiche; Georgios Stamatis; Dirk Theegarten; Hubertus Hautzel; Walter Jentzen; Nika Guberina; Ken Herrmann; Wilfried E E Eberhardt; Martin Stuschke

doi:10.2967/jnumed.120.260646

PROGNOSTIC VALUE OF POST-INDUCTION CHEMOTHERAPY VOLUMETRIC PET/CT PARAMETERS FOR STAGE IIIA/B NON-SMALL CELL LUNG CANCER PATIENTS RECEIVING DEFINITIVE CHEMORADIOTHERAPY

J Nucl Med. 2021 May 20;62(12):1684-1691. doi: 10.2967/jnumed.120.260646. Online ahead of print.

Authors

Maja Guberina¹, Christoph Poettgen¹, Martin Metzenmacher², Marcel Wiesweg², Martin Schuler³, Clemens Aigner⁴, Till Ploenes⁴, Lale Umutlu⁵, Thomas Gauler¹, Kaid Darwiche⁶, Georgios Stamatis⁴, Dirk Theegarten⁷, Hubertus Hautzel⁸, Walter Jentzen⁸, Nika Guberina¹, Ken Herrmann⁹, Wilfried E E Eberhardt¹⁰, Martin Stuschke¹¹

Affiliations

¹ Department for Radiotherapy, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany, Germany.
² 1. Department of Medical Oncology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany 2. Division of Thoracic Oncology, University Medicine Essen - Ruhrlandklinik, West German Cancer Center, Essen, Germany.
³ 1.Department ofMedicalOncology, UniversityHospital,WestGermanCancerCenter, UniversityDuisburg-Essen, 2.Division of Thoracic Oncology, UniversityMedicineEssen,Ruhrlandklinik,WGCC,University D.-E.; 3.GermanCancerConsortium,PartnerSiteUniversityHospitalEssen, Germany.
⁴ Department of Thoracic Surgery and Thoracic Endoscopy, University Medicine Essen - Ruhrlandklinik, West German Lung Center, University Duisburg-Essen, Essen, Germany, Germany.
⁵ Institute of Diagnostic and Interventional Radiology and Neuroradiology, University Hospital Essen, University Duisburg-Essen, Essen, Germany, Germany.
⁶ Department of Pulmonary Medicine, Section of Interventional Pneumology, University Medicine Essen - Ruhrlandklinik, West German Cancer Center, University Duisburg-Essen, Essen, Germany, Germany.
⁷ Institute of Pathology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany, Germany.
⁸ Department for Nuclear Medicine, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany, Germany.
⁹ 1. Department for Nuclear Medicine, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany; 2. German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany.
¹⁰ 1. Department of Medical Oncology, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany; 2. Division of Thoracic Oncology, University Medicine Essen-Ruhrlandklinik, West German Cancer Center, University D.-E.
¹¹ 1. Department for Radiotherapy, University Hospital Essen, West German Cancer Center, University Duisburg-Essen, Essen, Germany 2. German Cancer Consortium, Partner Site University Hospital Essen, Essen, Germany.

Abstract

Purpose/Objective(s): The aim of this follow-up analysis of the ESPATUE phase-3 trial was 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, SUV_max(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 SUV_max(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.

Keywords: Interim PET/CT; NSCLC stage III; Oncology: Lung; PET/CT; Radiation Therapy Planning; definitive radiotherapy; induction chemotherapy; prognostic value.