IBS14.02 Best Management of Early Stage NSCLC in ILD Patients

Abstract

Interstitial lung disease (ILD) is characterized by diffuse inflammation and fibrosis within the lung parenchyma.1Although a heterogeneous group of diseases, invariably, it is associated with a restrictive defect on pulmonary function testing, and a reduced ability for gas exchange.2 On imaging, features of ILD can include reticulation, traction bronchiectasis and honeycombing. Interestingly, a diagnosis of ILD is an independent risk factor for the development of lung cancer.3 Stereotactic ablative radiotherapy (SABR) is a common radical treatment modality for patients with early stage NSCLC and is characterized by its convenience, tolerability, and high efficacy.4 Given these features, it has been popularized as an attractive option in early stage NSCLC patients with significant medical co-morbidities. Early stage NSCLC patients with co-existing ILD, however, are a high-risk group for any type of treatment, both for treatment-related toxicities and for acute exacerbations of ILD. These toxicities can be severe, and in extreme scenarios, fatal. The focus of this abstract will be on the use of SABR for early stage NSCLC patients with ILD, with an aim to discuss emerging data and future research directions. Despite the generally favorable toxicity profile of SABR, there are an increasing number of reports of serious toxicities in patients with pre-existing ILD. These reports have largely been retrospective in nature, heterogeneous in the radiation doses employed, with findings of extreme ranges in treatment related death rates. Arguments can be made on whether some of these reports, especially in those with exceptionally high rates of extreme toxicity, confer an element of publication bias. This refers to the phenomenon whereby there is an inclination to report results that are more remarkable (i.e. major toxicity or treatment-related death). Therefore, although it is likely that SABR incurs a greater risk in this setting compared to standard lung SABR cases, the true risk is unclear. To further delve into this issue, our group recently performed a systematic review and meta-analysis of outcomes following several different treatment modalities for early-stage lung cancer patients with ILD.5 From this initiative, 13 studies assessing outcomes after SABR were identified, and recognizing the caveats of the available data, we concluded that there was a 1 in 4 risk of severe radiation pneumonitis (defined as grade ≥3), and a 15% risk of treatment-related grade 5 toxicity. A specific diagnosis of idiopathic pulmonary fibrosis (IPF) appeared to be associated with the greatest risk, whereby treatment related mortality was 1 in 3, as compared to 14% for non-IPF fibrotic ILD. When considering this potential increased risk, it is important to recognize that the IPF patient population has a significant background risk of acute exacerbations of their disease, with an annual reported range of 5-19%.6 The Canadian Pulmonary Radiotherapy Investigators group (www.capriclinicaltrials.com) has designed a single arm phase II trial to evaluate the role of SABR in T1-2N0M0 NSCLC patients with co-existing ILD who are not surgical candidates. The trial (clinicaltirals.gov, NCT03485378) is entitled: Assessment of Precision Irradiation in Early Non-Small Cell Lung Cancer and Interstitial Lung Disease (ASPIRE-ILD). To our knowledge, this will be the first prospective trial evaluating this clinical scenario, and it is novel in that patients will be stratified using the ILD-GAP score, which is an index that incorporates ILD mortality risk according to Gender, Age and Physiology.7 The starting SABR dose will be 50 Gy in 5 fractions, and the dose fractionation will be escalated or de-escalated depending on toxicities observed in different cohorts of the trial. The appropriateness of SABR in any, or some of these patients can certainly be questioned in light of the potential serious toxicity. On the other hand, the median survival of untreated stage I NSCLC has consistently been reported to be less than 1 year in various studies.8 Therefore, the value of treatment would ideally be answered through a randomized controlled trial, however, this is probably unfeasible as patients and physicians alike may be uncomfortable with randomization. Given the inherent risks of both untreated cancer as well as any cancer-directed treatment, we encourage investigators to continue to report on their experiences in this challenging clinical dillemma, whether positive or negative, so that additional research can inform shared decision making. REFERENCES 1. Maher EJ, Timothy A, Squire CJ, et al. Audit: the use of radiotherapy for NSCLC in the UK. Clin Oncol (R Coll Radiol)1993;5:72-79. 2. Bradley B, Branley HM, Egan JJ, et al. Interstitial lung disease guideline: the British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax2008;63 Suppl 5:v1-58. 3. Naccache JM, Gibiot Q, Monnet I, et al. Lung cancer and interstitial lung disease: a literature review. J Thorac Dis2018;10:3829-3844. 4. Louie AV, Palma DA, Dahele M, et al. 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