Postoperative radiotherapy after chemo-immunotherapy and surgery for stage III non-small cell lung cancer

Radiotherapy to Optimize Event-free Survival Following Chemo-Immunotherapy and Surgery in Upper Stage III NSCLC With Evidence of Pathological Residual Disease (RESCUE): Phase II Trial

This study tests whether adding postoperative radiotherapy to the involved lymph node regions helps people with stage III non-small cell lung cancer who still have cancer in their lymph nodes after neoadjuvant chemo-immunotherapy and surgery.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 118 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Centre hospitalier de l'Université de Montréal (CHUM) (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy
• Locations: 1 site (Montreal, Quebec)
• Trial ID: NCT06878274 on ClinicalTrials.gov

What this trial studies

This is a randomized phase II trial enrolling 118 patients with stage III NSCLC who have residual nodal disease following neoadjuvant chemo-immunotherapy and complete (R0) surgical resection. Participants are randomly assigned to receive postoperative radiotherapy (targeting involved lymph node regions) or no postoperative radiotherapy, with stratification by use of adjuvant immunotherapy. The primary endpoint is event-free survival, with secondary endpoints including overall survival, locoregional and distant control, toxicity, and quality of life, and follow-up extending up to five years. The trial is sized to detect a 15% absolute improvement in 2-year event-free survival and has an overall planned duration of about seven years.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed stage III NSCLC who received 2–4 cycles of neoadjuvant chemo-immunotherapy, underwent complete (R0) resection with mediastinal lymph node dissection, have residual nodal disease on final pathology, ECOG 0–2, no actionable driver mutations, and adequate lung function (FEV1 > 1 L) are ideal candidates.

Not a fit: Patients with a pathological complete response in the nodes (no residual nodal disease), those with actionable driver mutations, prior chest radiotherapy, poor lung function, metastatic disease, pregnancy, or who are more than 24 weeks from thoracic surgery are unlikely to benefit or are ineligible.

Why it matters

Potential benefit: If successful, adding postoperative radiotherapy could reduce the risk of recurrence and improve event-free and overall survival for patients with residual nodal disease after chemo-immunotherapy and surgery.

How similar studies have performed: Prior trials of postoperative radiotherapy in stage III NSCLC have shown mixed results, and use of PORT specifically after neoadjuvant chemo-immunotherapy is a relatively new approach with limited prior data.

Eligibility criteria

Inclusion Criteria:

1. Participants must be ≥ 18 years old
2. Ability to provide written informed consent
3. ECOG performance status 0-2
4. Histologically confirmed NSCLC
5. Absence of actionable driver mutation (EGFR/ALK/ROS)
6. Complete preoperative imaging staging, including: FDG-PET and brain imaging to exclude distant metastases will be mandatory.
7. Baseline clinical or post-operative pathological stage III including specifically stage T1-4N2-3
8. Completion of 2-4 cycles of neoadjuvant chemo-IO, regardless of the specific immunotherapy and chemotherapy used.
9. Status post-complete (R0) surgical resection with mediastinal lymph node dissection.
10. Residual nodal disease on final pathology specimen (i.e. absence of pathological complete response).
11. Postoperative lung function examination: FEV1 \> 1 L (or greater than 35% expected value)

Exclusion Criteria:

1. Pregnant individuals
2. Previous chest radiotherapy
3. \>24 weeks after thoracic surgery
4. History of other non-cutaneous neoplasms within the last 24 months
5. Active grade ≥ 2 pneumonitis.
6. Presence of interstitial lung disease
7. Recurrence or metastasis occurred
8. Medical conditions that hinders the safe administration of radiotherapy or follow-up.

Where this trial is running

Montreal, Quebec

• Centre Hospitalier de l'Université de Montréal — Montreal, Quebec, Canada (Recruiting)

Study contacts

• Study coordinator: Houda Bahig, MD PhD

Conditions Non Small Cell Lung Cancer; Stage III Lung Cancer; Post operative radiotherapy; lung cancer; non small cell lung cancer; stage III lung cancer; neoadjuvant immunotherapy