ESTRO 2024 - Abstract Book

S117

Invited Speaker

ESTRO 2024

3531

The NARLAL II trial: First results on loco-regional control in stage 3 NSCLC

Tine Schytte 1,2 , Charlotte Kristiansen 3 , Ane Appelt 4 , Azza Khalil 5 , Carsten Brink 6 , Christina Maria Lutz 5 , Ditte Slot Moeller 5 , Erland Sande 7 , Filippa Sundbye 8 , Gitte Persson 8 , Lone Hoffmann 5 , Lotte Holm Land 1 , Lotte Victoria Rogg 7 , Mette Poehl 9 , Mikkel Lund 3 , Morten Nielsen 6 , Nina Levin 10 , olfred Hansen 1 , Rune Slot Thing 3 , Tarje Halvorsen 10 , Tine Bjoern Nielsen 6 , Torben Schjødt Hansen 3 , Vilde Haakensen 7 , Wiviann Ottosson 8 , Marianne Knap 5 1 Odense University Hospital, Oncology, Odense, Denmark. 2 University of Southern Denmark, Clinical Research, Odense, Denmark. 3 Vejle Hospital, Oncology, Vejle, Denmark. 4 University of Leeds, Radiotherapy Research Office, Leeds, United Kingdom. 5 Aarhus University Hospital, Oncology, Aarhus, Denmark. 6 Odense University Hospital, Laboratory of radiation physics, Odense, Denmark. 7 Oslo University Hospital, Oncology, Oslo, Norway. 8 Herlev Hospital, Oncology, Herlev, Denmark. 9 Rigshospitalet, Oncology, Copenhagen, Denmark. 10 St Olav Hospital, Oncology, Trondheim, Norway The survival and loco-regional control for patients with locally advanced NSCLC (LA-NSCLC) are dismal despite the introduction of adjuvant durvalumab. Radiotherapy dose escalation may offer improved loco-regional control, but there have been serious concerns about dose escalation for these patients since the unexpected results on survival of the RTOG0617 trial particular when using standard uniform dose prescription principles. A novel approach to dose escalation is therefore warranted. A possible strategy is to combine the principles from stereotactic body radiotherapy (SBRT) with FDG-PET functional imaging to deliver highly heterogenous dose distributions. SBRT has demonstrated excellent local control in early-stage lung cancer. Single center data indicate that primary tumor site may be at highest risk of failure, with excellent control in mediastinal lymph nodes with standard (60-66 Gy) dose levels, indicating that it may not be necessary to escalate the dose to the lymph nodes as high as to the lung tumor. The international multicenter NARLAL2 ( N ovel A pproach to R adiotherapy for LA -NSC L C) phase III trial randomized patients with LA-NSCLC between standard 66Gy/33 fractions(F) versus heterogeneous FDG-PET driven dose escalation, aiming at mean dose to GTV-tumor PET 95 Gy/33F and mean dose to GTV-node PET 74Gy/33 F, while strictly respecting dose to organs at risk (OAR). The data on the primary endpoint, loco-regional control from this randomized trial is mature for analysis in March 2024, and will be presented at ESTRO 2024. The eligibility criteria for the NARLAL2 trial were age > 18 years, ECOG performance status 0-1, histological or cytological confirmed NSCLC stage IIB-IIIB, signed informed consent, and a clinically acceptable radiotherapy plan for homogeneously dosed 66Gy/33F. Patients were staged at multidisciplinary conference. PET-CT and brain MRI were part of staging. Patients were randomly assigned to either treatment group (1:1, stratified for center and histology). The trial aimed to have lung iso-toxicity between the arms by creating two radiotherapy plans (before randomization) for each patient, one for each arm with matching mean lung dose and lung V 20Gy . Abstract: Background Methods/material