Photo Credit: Dr Microbe
Researchers investigated the safety of SABR in a small population of patients with both NSCLC and ILD, who may have a greater risk for radiation damage.
Stereotactic ablative radiotherapy (SABR) is safe for patients who have both early-stage non-small cell lung cancer (NSCLC) and fibrotic interstitial lung disease (ILD), according to results from a small study published in JAMA Oncology.
“The use of SABR in patients with ILD met prespecified acceptability thresholds for both toxicity and efficacy, supporting the use of SABR for curative-intent treatment after a careful discussion of risks and benefits,” lead study author David A. Palma, MD, PhD, MSc, FRCPC, and colleagues wrote.
Limited Treatment Options
SABR has a favorable toxicity profile and is the preferred treatment for frail patients with early-stage NSCLC, such as older adults and those with poor lung function who are unable or unwilling to have parts of their lung surgically removed. However, similar mechanisms appear to cause radiotherapy-induced lung damage and ILD fibrosis, which increases the risk of radiation damage for patients with both early-stage NSCLC and ILD. Therefore, investigators assessed the survival outcomes and toxic effects of SABR in patients with both conditions.
The researchers conducted an open-label, phase 2 clinical trial titled ASPIRE-ILD. Between March 2019 and January 2022, they enrolled 39 adult participants with early-stage (T1-2N0) NSCLC and fibrotic ILD who were not eligible for surgical resection. Patients were treated at five academic radiation oncology sites in Canada and one in Scotland.
The median participant age was 78 years, and 59% were male. At baseline, 70% reported dyspnea, the median forced expiratory volume in the first second of expiration (FEV1) was 80% predicted, the median forced vital capacity (FVC) was 84% predicted, and the median diffusion capacity of the lung for carbon monoxide (DLCO) was 49% predicted.
The researchers prespecified that SABR would be considered worthwhile if the median overall survival was longer than 1 year, with less than 35% risk for grade 3-4 AEs and less than 15% risk for grade 5 AEs.
Acceptable Efficacy and Toxicity
Participants received 50 Gy of SABR in 5 fractions every other day. The median follow-up was 19 months.
At 1 year, the rate of overall survival was 79% (95% CI, 62%-89%; P<0.001 vs the unacceptable rate), and median overall survival was 25 months (95% CI, 14 months to not reached). Progression-free survival at 1 year was 74% (95% CI, 57%-85%), and median progression-free survival was 19 months (95% CI, 13-28 months).
At 2 years, local control was 92% (95% CI, 69%-98%), regional control was 86% (95% CI, 60%-95%), and distant control was 91% (95% CI, 64%-98%).
AE rates were recorded as the highest grade per patient. Twelve patients (30.8%) experienced grade 1-2 AEs; 4 (10.3%) experienced grade 3 AEs; and 3 (7.7%) experienced grade 5 AEs, all attributable to respiratory deterioration. Grade 4 AEs did not occur in any patients.
Increased Access to Care
The magnitude of the survival benefit surprised Ticiana Leal, MD, who was not involved in the study.
“This study implemented the careful planning of SABR, the use of a minimum SABR dose, and the assessment and follow-up by pulmonary, which could explain the better outcomes with acceptable toxicities [compared to earlier data in the literature]. The careful pulmonary follow-up may have positively impacted the results, highlighting the importance of a multidisciplinary approach to the care of these patients,” says Dr. Leal.
“The strength of the study is that it addresses a gap in care for patients with inoperable early-stage NSCLC and ILD who have limited to no treatment options for their lung cancer,” she says, adding that limitations include the non-randomized design and small sample size.
Alexander Chin, MD, MBA, who also was not involved in the research, was surprised by the relatively low toxicity rate in this study compared with existing data, “especially given the broad attribution of respiratory events to radiotherapy in the study.”
“Existing data on the safety of SABR in patients with ILD are sparse and often include heterogeneous patient populations and a variety of radiotherapy doses, fractionation, and planning protocols,” Dr. Chin explains. “This study standardizes those parameters prospectively to better elucidate the impact of high-dose lung radiotherapy on respiratory outcomes in this small but important subset of patients.”
Further Research Needed
“This study provides the highest-quality data to date on the risks and benefits of SABR in patients with ILD,” Dr. Chin says. “However, the degree to which certain clinical factors, such as ILD subtype and severity, interact with dosimetric parameters to influence the risk for toxicity remains unclear.”
Both experts advised further research. Dr. Leal recommended randomized trials with more participants to investigate factors, including the impact of cardiovascular comorbidities, immunosuppression use, and ILD classification and severity.
Dr. Leal and Dr. Chin expect these high-quality results to inform clinicians’ conversations with their patients and improve patient access to a treatment they may be considered ineligible for.
