Introducing FDG PET/CT-guided chemoradiotherapy for stage III NSCLC in low- and middle-income countries: preliminary results from the IAEA PERTAIN trial

Abstract

Purpose Patients with stage III non-small-cell lung cancer (NSCLC) treated with chemoradiotherapy (CRT) in low- and middle-income countries (LMIC) continue to have a poor prognosis. It is known that FDG PET/CT improves staging, treatment selection and target volume delineation (TVD), and although its use has grown rapidly, it is still not widely available in LMIC. CRT is often used as sequential treatment, but is known to be more effective when given concurrently. The aim of the PERTAIN study was to assess the impact of introducing FDG PET/CT-guided concurrent CRT, supported by training and quality control (QC), on the overall survival (OS) and progression-free survival (PFS) of patients with stage III NSCLC. Methods The study included patients with stage III NSCLC from nine medical centres in seven countries. A retrospective cohort was managed according to local practices between January 2010 and July 2014, which involved only optional diagnostic FDG PET/CT for staging (not for TVD), followed by sequential or concurrent CRT. A prospective cohort between August 2015 and October 2018 was treated according to the study protocol including FDG PET/CT in treatment position for staging and multimodal TVD followed by concurrent CRT by specialists trained in protocol-specific TVD and with TVD QC. Kaplan–Meier analysis was used to assess OS and PFS in the retrospective and prospective cohorts. Results Guidelines for FDG PET/CT image acquisition and TVD were developed and published. All specialists involved in the PERTAIN study received training between June 2014 and May 2016. The PET/CT scanners used received EARL accreditation. In November 2018 a planned interim analysis was performed including 230 patients in the retrospective cohort with a median follow-up of 14 months and 128 patients in the prospective cohort, of whom 69 had a follow-up of at least 1 year. Using the Kaplan–Meier method, OS was significantly longer in the prospective cohort than in the retrospective cohort (23 vs. 14 months, p = 0.012). In addition, median PFS was significantly longer in the prospective cohort than in the retrospective cohort (17 vs. 11 months, p = 0.012). Conclusion In the PERTAIN study, the preliminary results indicate that introducing FDG PET/CT-guided concurrent CRT for patients with stage III NSCLC in LMIC resulted in a significant improvement in OS and PFS. The final study results based on complete data are expected in 2020. Electronic supplementary material The online version of this article (10.1007/s00259-019-04421-5) contains supplementary material, which is available to authorized users.

Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III NSCLC: Results of KINDLE, a Multicountry Observational Study

“…[23][24][25] Preliminary results of an ongoing multicenter, international PERTAIN study suggest significantly improved PFS (17.0 versus 11.0 mo) and OS (23.0 versus 14.0 mo [p ¼ 0.012 for both]) with fluorodeoxyglucose positron emission tomography/CT-guided cCRT compared with routine diagnosis followed by sequential or cCRT. 26 In our study, although the number of patients receiving triple therapy (surgery þ CRT) was small (<2%), they had significantly longer survival. This is in line with some recent studies wherein triple therapy regimens have revealed significant survival benefits compared with CRT alone as initial therapy.…”

Challenges of radical chemoradiation planning in Stage III non-small-cell lung cancer: Can volumetric modulated arc radiotherapy overcome an unfavourable location?

“…With more PET-CT availability, usage of this modality in both staging and treatment planning is on the rise. Preliminary results show a significant improvement in OS (23 months) when compared to historical data by using strictly regulated PET-CT based planning [10] .…”

“…As part of the international collaborative PERTAIN (PET RadioTherApy International, NCT02247713) study, Stage III NSCLC patients were treated with concurrent chemoradiotherapy (CRT) based on PET-CT based imaging in the treatment position. This dosimetric analysis was done on the side-lines of PERTAIN to analyse tumour and nodal characteristics in the subset of patients excluded from the study due to inability to plan and deliver doses till 60 Gy in view of critical organ constraints [10] . Alternate Volumetric Modulated Arc Radiotherapy (VMAT) plans were made for patients treated by 3D-CRT to identify the subset of patients where using a different radiotherapy technique might address this shortcoming.…”

“…due to inability to plan and deliver doses till 60 Gy in view of critical organ constraints [10]. Alternate Volumetric Modulated Arc Radiotherapy (VMAT) plans were made for patients treated by 3D-CRT to identify the subset of patients where using a different radiotherapy technique might address this shortcoming.…”

Global Radiotherapy: Current Status and Future Directions—White Paper

“…Biologic target delineation based on fluorodeoxyglucose positron emission tomography-computed tomography treatment planning is routine practice at present in many departments, but new tracers and other imaging modalities like positron emission tomography-magnetic resonance imaging will define new signatures and molecular targets for treatment. 61 , 62 …”