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Alexander Vincent Louie
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IBS14 - Best Management of Early Stage NSCLC in ILD Patients (Ticketed Session) (ID 45)
- Event: WCLC 2019
- Type: Interactive Breakfast Session
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/09/2019, 07:00 - 08:00, Melbourne (1991)
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IBS14.02 - Best Management of Early Stage NSCLC in ILD Patients (Now Available) (ID 3358)
07:00 - 08:00 | Presenting Author(s): Alexander Vincent Louie
- Abstract
- Presentation
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. Management of early-stage non-small cell lung cancer using stereotactic ablative radiotherapy: Controversies, insights, and changing horizons. Radiother Oncol2015;114:138-147.
5. Chen H, Senan S, Nossent EJ, et al. Treatment-Related Toxicity in Patients with Early-Stage Non-Small Cell Lung Cancer and Co-Existing Interstitial Lung Disease: A Systematic Review. International Journal of Radiation Oncology*Biology*Physics.
6. Hyzy R, Huang S, Myers J, et al. Acute exacerbation of idiopathic pulmonary fibrosis. Chest2007;132:1652-1658.
7. Milne KM, Kwan JM, Guler S, et al. Frailty is common and strongly associated with dyspnoea severity in fibrotic interstitial lung disease. Respirology2017;22:728-734.
8. Nanda RH, Liu Y, Gillespie TW, et al. Stereotactic body radiation therapy versus no treatment for early stage non-small cell lung cancer in medically inoperable elderly patients: A National Cancer Data Base analysis. Cancer2015.
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P1.17 - Treatment of Early Stage/Localized Disease (ID 188)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment of Early Stage/Localized Disease
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.17-21 - Safety and Effectiveness of Stereotactic Ablative Radiotherapy for Ultra-Central Lung Lesions: A Systematic Review (Now Available) (ID 1136)
09:45 - 18:00 | Author(s): Alexander Vincent Louie
- Abstract
Background
The safety and effectiveness of stereotactic ablative radiotherapy (SABR) for patients with ultra-central lung tumours is currently unclear. We performed a systematic review to summarize existing data and identify trends in treatment-related toxicity and local control following SABR in patients with ultra-central lung lesions.
Method
We performed a systematic review using the PRISMA guidelines. The PubMed and Embase databases were queried from dates of inception until September 2018. Studies in the English language that reported treatment-related toxicity and local control outcomes post-SABR for patients with ultra-central lung lesions were included. Ultra-central lung lesions were defined as lesion whose gross tumour volume (GTV) or planning target volume (PTV) abutted or invaded the proximal tracheo-bronchial tree (PBT) or other mediastinal structures such as the great vessels or esophagus. Guidelines, reviews, non-peer reviewed correspondences, studies focused on re-irradiation and studies with fewer than 5 patients were excluded.
Result
A total of 446 studies were identified, with 10 meeting all criteria for inclusion. The total sample size from the identified studies was 250 patients with ultra-central lung lesions and all studies were retrospective in design. Six out of the 10 studies included a majority (>50%) of primary lung cancers. Radiotherapy dose and fractionation ranged from 30 to 60 Gy in 3 to 12 fractions, with biologically-effective doses (BED10) ranging from 48 to 138 Gy10 (median 78-103 Gy10). Median treatment-related grade >3 toxicity was 10% (range: 0-50%). Median treatment-related mortality was 5% (range: 0-22%), most commonly from pulmonary hemorrhage (55%). High-risk indicators for SABR-related mortality included gross endobronchial disease, maximum dose to the proximal bronchial tree (PBT) >180 Gy3 (BED3, corresponding to 45 Gy in 5 fractions or 55 Gy in 8 fractions), peri-SABR bevacizumab use, and antiplatelet/anticoagulant use. Median 1-year local control rate was 96% (range: 63-100%) and 2-year local control rate was 92% (range: 57-100%).
Conclusion
SABR for ultra-central lung lesions appears feasible and local control levels are comparable to those found in SABR for central lung lesions. There is a potential for severe toxicity in delivering SABR to ultra-central lung lesions especially in patients receiving high doses to the PBT, patients with endobronchial disease, and patients receiving bevacizumab or anticoagulants around the time of SABR. Prospective studies are required to establish the optimal doses, volumes and normal tissue tolerances for SABR in this patient population.
