# Accelerated vs. conventionally fractionated postoperative radiotherapy of non-small cell lung cancer—final results of the prematurely terminated PORTAF trial

## TL;DR

A clinical trial comparing fast vs. slow radiation therapy schedules after lung cancer surgery found no significant difference in cancer control.

## Contribution

The study prospectively tested accelerated vs. conventional fractionation in postoperative lung cancer radiotherapy using a randomized trial.

## Key findings

- Locoregional tumor control was not significantly different between accelerated (73%) and conventional (92%) fractionation.
- FDG-PET/CT restaging revealed unexpected recurrences and metastases, suggesting its potential for better patient selection.
- The trial was prematurely closed due to slow enrollment and changing treatment practices.

## Abstract

A prolonged overall treatment time (OTT) has been demonstrated to adversely affect the primary radiation therapy (RT) outcome in various solid tumors, including non-small cell lung cancer (NSCLC). Retrospective data from our group suggested an advantage of shorter OTT also for postoperative RT (PORT) in patients with NSCLC. The PORTAF trial (ClinicalTrials.gov: NCT02189967) was initiated to prospectively test this hypothesis.

The multicenter prospective randomized phase II trial in patients with NSCLC investigated whether an accelerated schedule of PORT (7 fractions per week, 2 Gy per fraction, OTT 3.5–4 weeks) improved outcome compared to conventional fractionation (5 fractions per week, 2 Gy per fraction, OTT 5–6 weeks). Target volumes and total radiation doses were stratified in both treatment arms based on individual risk factors. Primary endpoint of the study was locoregional tumor control (LRTC) 36 months after PORT, with 154 patients to be included in each arm.

Due to slow accrual and changed indications for PORT, we prematurely closed the trial in 2019. Between 2014 and 2019, eight recruiting centers included 27 evaluable patients. An interim safety analysis performed for the first 21 patients showed nonsignificant differences regarding grade 3 toxicities between the treatment arms, thus not meeting the termination criteria. LRTC was not significantly different between accelerated (73%) and conventionally fractionated RT (92%; p = 0.535). Noteworthily, in 21 FDG-PET/CT restagings before RT, an unexpectedly high number of locoregional recurrences (n = 4) and distant metastases (n = 2) were seen, resulting in changed treatment intentions for these patients.

The prematurely closed PORTAF trial did not find significant differences in 3‑year LRTC when comparing accelerated versus conventionally fractionated irradiation. The observed additional benefit of FDG-PET/CT restaging prior to PORT should be further investigated in a larger cohort to optimize patient selection and avoid unnecessary side-effects.