Upfront Resection of Locally-Advanced and/or Cavitating NSCLC Followed by Chemoradiotherapy (and adjuvant systemic treatment); Phase 1 multicenter study to assess treatment feasibility and Safety (NVALT32/ UPLAN-I Trial) – Study protocol

Author(s): PJM Joosten, RG Luger, V. Van der Noort, W.S.M.E. Theelen, M.C. De Jong, K. Monkhorst, A.F.T.M. Verhagen, M.M. Van den Heuvel, A.C. Dingemans, A.P.W.M. Maat, L.E.L. Hendriks, M. Hutteman, A.J. Van der Wekken, A.M. Slats, E.F. Smit, and K.J. Hartemink

Background: Standard treatment of stage III non-small cell lung cancer (NSCLC) with multilevel/bulky N2 or N3 disease is chemoradiotherapy (CRT) followed by immune checkpoint inhibition (ICI, durvalumab). However, no separate recommendations are made for large volume or cavitating tumors, in which infectious complications, bleeding and a high local recurrence rate is frequently seen after treatment with CRT. Upfront resection of a (potentially) resectable large volume and/or cavitating primary lung tumor in patients with extensive stage III NSCLC, followed by CRT could be a strategy to prevent complications of CRT

Methods/Design: A multicenter feasibility study, enrolling 20 patients with cT3-4N2M0 NSCLC with cavitation or large volume of the primary tumor and/ or multilevel or bulky N2 disease, or patients with cT3- 4N3M0 disease with a resectable primary tumor. An upfront resection of the primary tumor is followed by CRT (and adjuvant ICI if indicated). The primary study objective is feasibility assessed by the number of patients completing the predefined treatment (upfront resection + CRT). Secondary objectives are safety and complications.

Conclusion: The potential advantages, e.g. reduction of radiotherapy treatment volumes, improved local control and reduction of long-term infectious problems or bleeding complications after upfront resection of the large volume or cavitating lung tumor, may outweigh the complications resulting from surgery and the risk of a delayed start of the standard of care treatment. In this study, we aim to evaluate feasibility and safety of upfront resection of the
primary lung tumor, followed by CRT in this NVALT32/ UPLAN-I trial.