New study examines safety and effectiveness of stereotactic radiotherapy in NSCLC with ILD

Non-small cell lung cancer (NSCLC) accounts for the majority of lung cancer diagnoses and is frequently diagnosed in older adults. Surgical resection remains the preferred approach for early-stage disease, but many patients are medically inoperable because of limited pulmonary reserve or underlying lung conditions.

Stereotactic ablative radiotherapy, also referred to as stereotactic body radiation therapy, has emerged as a standard noninvasive alternative, offering high local control rates with relatively limited toxicity in carefully selected patients. However, individuals with interstitial lung disease have long posed a clinical challenge.

A new study conducted by researchers at Queen Elizabeth Hospital Birmingham in Birmingham, Great Britain, evaluated outcomes and toxicity associated with stereotactic radiotherapy in patients with early-stage, non-small cell lung cancer and co-existing interstitial lung disease (ILD).

The researcher, led by Alexander Sherlock, M.B.B.S., and Annalise M. Tanaka, M.B.B.S., explained ILD is associated with fragile lung parenchyma and heightened susceptibility to treatment-related injury, particularly radiation pneumonitis.

As a result, patients with ILD have often been excluded from prospective stereotactic radiotherapy trials, leaving clinicians to rely on limited observational data when making treatment decisions for this high-risk population.

In their study, published Dec. 26 in Cureus, Sherlock, Tanaka and colleagues analyzed patients with early-stage non-small cell lung cancer and radiographically confirmed ILD treated with stereotactic radiotherapy across four centers in the United Kingdom between February 2020 and May 2025.

All patients were considered not suitable for surgical treatment and were treated with curative intent using ILD-adapted stereotactic radiotherapy regimens.

Radiotherapy planning and dose fractionation were modified to reduce pulmonary toxicity risk, reflecting institutional practices for patients with underlying fibrotic lung disease. Baseline data included age, smoking history, lung function, tumor characteristics and ILD subtype when available.

Of interest to the researchers were overall survival, local tumor control and treatment-related toxicity, with particular attention to clinically significant pulmonary adverse events.

Based on the findings, the study demonstrated that stereotactic radiotherapy achieved favorable local control in this high-risk cohort. Most treated tumors remained locally controlled at last follow-up, suggesting that oncologic effectiveness was largely preserved despite dose adaptations and the presence of interstitial lung disease.

The findings align with prior reports supporting stereotactic radiotherapy as an effective local treatment for early-stage non-small cell lung cancer in medically inoperable patients.

Toxicity outcomes reflected the known vulnerability of patients with interstitial lung disease. Rates of radiation pneumonitis were higher than those typically reported in unselected stereotactic radiotherapy populations, and a subset of patients experienced grade 3 or higher pulmonary toxicity.

Symptoms included worsening dyspnea and cough, with some cases requiring hospitalization and systemic therapy. Lower-grade pulmonary symptoms were also common and were sometimes difficult to distinguish from the progression of underlying ILD.

Despite these risks, many patients completed treatment without severe complications, and overall survival outcomes were consistent with expectations for early-stage non-small cell lung cancer treated nonsurgically.

The authors emphasized that while toxicity risk is increased, it is not universal, underscoring the importance of individualized risk assessment rather than blanket exclusion of patients with ILD from stereotactic radiotherapy consideration.

The study’s retrospective design limits causal inference, and the relatively small sample size reflects the rarity of patients with both early-stage lung cancer and clinically significant interstitial lung disease.

Additionally, ILD encompasses a heterogeneous group of disorders, and differences in ILD subtype, extent of fibrosis and baseline lung function may influence treatment tolerance and outcomes. These factors could not be fully accounted for in the analysis.

Even so, the findings add meaningful data to an area where evidence has been sparse. For clinicians, the results support stereotactic radiotherapy as a potential treatment option for select patients with early-stage non-small cell lung cancer and interstitial lung disease when surgery is not feasible.

“Careful patient selection, multidisciplinary evaluation and adapted radiotherapy planning remain critical to balancing cancer control with pulmonary safety,” the researchers wrote.