SABR Likely Safe, Effective for Patients Who Have NSCLC, ILD

Toxicity and efficacy thresholds were not crossed in a new analysis of the use of stereotactic ablative radiotherapy (SABR) 50 Gy in 5 fractions every other day in a patient population living with interstitial lung disease (ILD) and early-stage non–small cell lung cancer (NSCLC), indicating the treatment can continue to be used with curative intent in this patient population following “a careful discussion of risks and benefits.”

An image of lung cancer | Image Credit: utah51 - stock.adobe.com

Study findings from this analysis of data from the ASPIRE-ILD trial (NCT03485378) recently were published online in JAMA Oncology.¹ With previous research showing this patient population has a high toxicity risk after SABR—a procedure in which intense radiation treatment is concentrated on tumor tissue to minimize damage to surrounding organs²—the investigators used a median overall survival (OS) end point of 1 year and 35% and 15% risk levels for grade 3/4 and grade 5 toxic effects, respectively, to evaluate the treatment. All of the patients had T1-2N0 NSCLC and were not surgical candidates and could have Eastern Cooperative Oncology Group scores of 0 to 3. They were enrolled from 5 sites in Canada and 1 site in Scotland (N = 42; 39 received SABR and 3 chose observation), and data were gathered from March 7, 2019, to January 12, 2022; the end of follow-up was January 24, 2023. The median (IQR) patient age was 78 (67-83) years, 41% were female patients, and 92% had a smoking history.

“Patients with fibrotic [ILD] have been recognized as a subgroup of patients who may be at higher risk of severe radiation pneumonitis than the general population,” they wrote. “[ILD] and radiotherapy-associated lung damage share common pathways of lung injury, which may explain the elevated risks of radiation in this patient population.”

Overall at baseline, 825 of the patients had ILD-associated symptoms, including dyspnea, cough, reduced exercise tolerance, and general weakness. Their median forced vital capacity (FVC) was 84% (69%-94%); median forced expiratory volume in first second of expiration (FEV₁), 80% (66%-90%); and median diffusing capacity for carbon monoxide (DLCO), 49% (38%-61%). ILD was classified as unclassifiable or other subtype in 54%, and ILD severity was moderate in most.

The median follow-up was 19 (14-25) months, and during this time, 79% (95% CI, 62%-89%; P < .001) of the patients survived at least 1 year and 17 patients died. At 1 year, progression-free survival (PFS) was 74% (95% CI, 57%-85%), while the median PFS was 19 (95% CI, 13-28) months. Depending on ILD subtype, OS ranged from 62.5% (95% CI, 22.9%-86.1%) to 100% (95% CI, 100%-100%; P = .02) and PFS from 50% (95% CI, 15.2%-77.5%) to 100% (95% CI, 100%-100%; P = .03). At 2 years, local disease control was 92% (95% CI, 69%-98%), regional control was 86% (95% CI, 60%-95%), and distant control, 91% (95% CI, 64%-98%).

The highest adverse event (AE) grade was 1/2 in 30.8%, grade 3 in 10.3%, and grade 5 in 7.7%; none reported a grade 4 AE, and all of the grade 5 AEs were due to respiratory deterioration. Of the 17 recorded deaths, 14 were said to have cardiac causes and were not related to SABR.

Quality of life was evaluated using the Functional Assessment of Cancer Therapy-Lung scale, and there were significant decreases in both the social well-being and functional well-being subdomains. Social well-being scores fell approximately 0.41 (95% CI, −0.78 to −0.04; P = .03) points, and functional well-being, 0.52 (95% CI, −0.99 to −0.04; P = .03) points. In addition, cough severity worsened, DLCO and FVC decreased, and FEV¹ remained stable.

Of the 3 patients who elected observation, 2 died during the year-long follow-up and 1 remained alive at 25 months. Their median OS was 13 (8.4-19) months.

“In this population of patients with ILD and early-stage NSCLC, SABR was associated with a median survival more than double the expected median survival in untreated patients, meeting the primary end point of the trial,” the study authors wrote. “The observed risk of grade 3 to 5 toxic effects was approximately half of the risk reported in a prior systematic review.”

They attribute these results to their trial’s features: SABR was carefully planned and administered at a minimum dose, and respirology was closely monitored and assessed.

Potential limitations on their findings include the small patient population, which precludes generalizability to other disease subgroups; that the ILD subtype was unclassified in most; and only 3 patients chose observation.

The authors recommend that future studies should evaluate pharmacologic options that can help to reduce radiotherapy-induced toxic effects in these patients.

References

1. Palma DA, Bahig H, Hope A, et al. Stereotactic radiation therapy in early non–small cell lung cancer and interstitial lung disease: a nonrandomized clinical trial. JAMA Oncol. Published online March 7, 2024. doi:10.1001/jamaoncol.2023.7269
2. Stereotactic ablative radiotherapy (SABR/SBRT). Stanford Medicine. Accessed March 11, 2024. https://tinyurl.com/2nmut9wf