Patients with early-stage lung cancer and interstitial lung disease represent one of the most difficult groups to treat. These patients face two competing risks: progression of lung cancer and worsening of underlying lung disease.
A new real-world study published in Radiotherapy and Oncology compared outcomes after stereotactic ablative radiotherapy and surgery in patients with stage I–II lung cancer and coexisting interstitial lung disease.
The findings suggest that both SABR and surgery can be feasible curative-intent options in carefully selected patients, and that interstitial lung disease alone should not automatically exclude patients from local treatment.
Why This Study Matters
Interstitial lung disease includes a broad group of disorders characterized by inflammation, fibrosis, and scarring of the lung tissue. Patients with fibrotic ILD have a higher risk of developing lung cancer and often have worse survival than patients without ILD.
Treating lung cancer in this setting is challenging.
Surgery can increase the risk of postoperative pulmonary complications and acute ILD exacerbation. SABR is often used in patients who are less fit for surgery, but it can also cause radiation pneumonitis and may trigger ILD worsening.
Because both options carry risks, careful treatment selection is essential.
Study Design
This was a single-center retrospective study from a tertiary referral center with a dedicated multidisciplinary program for patients with lung cancer and ILD.
The study included adults with stage I–II lung cancer and confirmed coexisting ILD treated between 2006 and 2024.
All patients underwent multidisciplinary assessment involving thoracic oncology and ILD specialists, including radiation oncologists, surgeons, pulmonologists, radiologists, and pathologists.
Curative-intent treatment included either surgery or SABR.
The main outcomes were progression-free survival and overall survival. The investigators also evaluated local control, locoregional progression, distant progression, pulmonary adverse events, and prognostic factors.
Patient Population
A total of 67 patients with stage I–II lung cancer and ILD received curative-intent treatment.
Thirty-three patients underwent surgery, and 34 received SABR.
Patients treated with surgery were generally younger and had better performance status. The SABR group included older and less fit patients, reflecting real-world treatment selection.
Idiopathic pulmonary fibrosis was present in 24% of surgical patients and 38% of patients treated with SABR.
Stage II disease was also more common in the SABR group.
Treatment Details
Among surgical patients, most underwent minimally invasive procedures. Video-assisted thoracoscopic surgery was used in 73% of cases, including uniportal VATS in one-third of patients.
The surgical procedures included lobectomy, wedge resection, and segmentectomy.
Among patients treated with SABR, several dose schedules were used. The most common regimens were 60 Gy in 8 fractions and 55–60 Gy in 5 fractions.
Nearly half of SABR patients received MR-guided treatment, reflecting evolving practice and the use of motion-managed radiotherapy.
Survival Outcomes
Median follow-up was 40 months.
Two-year progression-free survival was 54% after surgery and 53% after SABR.
Two-year overall survival was 68% after surgery and 56% after SABR.
In unadjusted analysis, surgery showed numerically longer overall survival, but this did not reach statistical significance.
After inverse probability of treatment weighting to adjust for baseline differences between the groups, no significant differences were observed between surgery and SABR for either progression-free survival or overall survival.
This is clinically important because SABR achieved comparable adjusted outcomes despite being used in an older and less fit population.
Local and Distant Control
SABR achieved high local tumor control.
Local control after SABR was 92% at 1 year, 88% at 2 years, and 80% at 3 years.
In the surgery group, local control was 86% at 1 year, with no further local progression at 2 or 3 years.
Locoregional and distant progression-free survival were numerically similar between the two treatment approaches, without statistically significant differences.
Pulmonary Adverse Events
Pulmonary toxicity is a central concern when treating patients with ILD.
In this cohort, 16 pulmonary adverse events occurred in 14 patients, representing 21% of the study population.
These included ILD exacerbations, postoperative complications, and radiation pneumonitis.
Three patients experienced treatment-related ILD exacerbation. One occurred after surgery, and two occurred after SABR.
Surgical complications occurred in six patients.
Radiation pneumonitis occurred in seven patients, including grade 2, grade 3, and grade 5 events.
Overall, pulmonary adverse event rates were not significantly different between surgery and SABR.
Risk Factors for Worse Outcomes
The most important prognostic factor was progressive pulmonary fibrosis.
In multivariable analysis, progressive pulmonary fibrosis was independently associated with worse overall survival and worse progression-free survival.
This suggests that ILD behavior and subtype may be more important for prognosis than the choice between surgery and SABR alone.
Other factors associated with poorer outcomes in univariable analysis included older age, worse performance status, idiopathic pulmonary fibrosis, higher GAP index, and reduced lung function.
For pulmonary adverse events, worse performance status, idiopathic pulmonary fibrosis, and lower forced vital capacity were associated with higher risk.
Clinical Interpretation
This study supports a practical and nuanced message.
Patients with early-stage lung cancer and ILD should not be denied curative treatment simply because ILD is present.
Instead, treatment decisions should be individualized through multidisciplinary assessment.
For patients who are fit for surgery, surgical resection remains an important option. For older, frailer, or medically inoperable patients, SABR may provide comparable disease outcomes with an acceptable toxicity profile.
The findings also highlight the importance of identifying patients with progressive pulmonary fibrosis, because this phenotype was strongly linked to worse outcomes.
Limitations
The study was retrospective and included a relatively small number of patients.
Treatment selection was not randomized, meaning that the surgery and SABR groups differed at baseline.
Although the investigators used statistical adjustment, residual confounding remains possible.
The cohort also included different ILD subtypes, tumor histologies, surgical approaches, and SABR regimens.
Toxicity assessment was retrospective, and some events may have been underrecognized, especially in patients followed at referring hospitals.
Despite these limitations, the study provides valuable real-world evidence for a population that is often excluded from clinical trials.
Clinical Takeaway
SABR and surgery both appear to be feasible curative-intent treatment options for selected patients with stage I–II lung cancer and interstitial lung disease.
After adjustment for baseline differences, no significant survival difference was observed between the two approaches.
Pulmonary adverse events occurred but were not significantly different between surgery and SABR.
The strongest prognostic signal was progressive pulmonary fibrosis, which was associated with worse survival outcomes.
The key message is clear: interstitial lung disease should not automatically preclude curative treatment in early-stage lung cancer.
For these high-risk patients, the best approach is individualized decision-making through a multidisciplinary ILD and thoracic oncology team.
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