ED08.02 The Role of Radiotherapy in Early-Stage NSCLC

Abstract

Radiotherapy is a curative treatment for early-stage NSCLC. Following hypofractionated radiotherapy in 15 once-daily fractions of 4 Gy to biopsy-proven tumors, a prospective multicenter study reported a 3-year local control rate of 82.7% (95% CI = 69.7% to 90.5%) [Cheung PC, 2014]. In the past decade, stereotactic ablative radiotherapy (SABR or SBRT) has become established as the guideline-recommended standard of care for medically inoperable patients with a peripheral early-stage NSCLC, as 5-year local control rates of 90% have been reported [Louie AV, 2015]. SABR is usually delivered in 3-8 fractions, utilizes small margins for positional uncertainty, 4-dimensional computed tomography (4DCT) for treatment planning, multiple conformal beams or arcs for delivery, and cone-bean CT scans for daily setup. Where facilities for SABR are unavailable, hypofractionated radiotherapy delivered using 4DCT planning remains an acceptable curative treatment. Population studies reveal that a significant proportion of elderly patients, as well as those with severe co-morbidities, do not receive any treatment. Guidelines recommend that a tissue diagnosis be obtained before initiating treatment for early-stage NSCLC, but also permit the use of SABR following review by an expert tumor board, in tumors where the calculated probability of malignancy is high [Vansteenkiste J, 2014; Callister ME, 2015]. However, any decision to proceed to a FDG-PET directed SABR approach in less fit patients must take into account the likelihood of benign disease. Given a high incidence of pulmonary tuberculosis, guidelines for Asia have recommended performing early non-surgical biopsies in Asian patients [Bai C, 2016]. Treatment-related grades 3-4 toxicity are uncommon following SABR to peripheral lung tumors, while local control rates are approximately 90% [Louie AV 2015]. Commonly reported toxicities are chest wall pain, rib fractures, and except in patients who have pre-existing interstitial lung disease (ILD), the incidence of high-grade radiation pneumonitis is low. A systematic literature review of SABR in patients with ILD reported a treatment-related mortality in 15% [Chen H, Proc ASTRO 2016]. Guidelines recommend 6-monthly CT scans for up to 3 years following SABR, followed by annual scans thereafter. The assessment of radiological changes can be challenging in a sub-group of patients during long-term follow-op, and the so-called high-risk radiological features [HRF] can identify patients in whom a biopsy is warranted [Figure 1, Huang K, 2014]. The HRF’s identified in the literature are an enlarging opacity at primary site, a sequential enlarging opacity, enlarging opacity after 12-months, a bulging margin, loss of linear margin, loss of air bronchogram and cranio-caudal growth [Huang K, 2014]. Initial reports on surgery for local failures following SABR indicate that this salvage procedure can be performed safely [Allibhai Z, 2012; Hamaji M, 2015; Verstegen N, Proc ELCC 2015]. The observed rates for a second primary lung cancer following SABR appear similar to those following surgery [Verstegen N, 2015]. In this situation, a subsequent course of SABR can generally be performed safely. The role of SABR in fit patients remains a topic of active debate. Indirect comparisons of outcomes following the two modalities have revealed conflicting results. The role of SABR in surgical patients is currrently being investigted in 3 prospective randomized studies (NCT02468024, NCT02629458, NCT01753414), with a fourth study (VALOR) scheduled to open shortly. stereotactic radiotherapy, Early-stage lung cancer, follow-up, toxicity