Stereotactic Ablative Radiotherapy Before Resection to AvoId Delay for Early-Stage LunG Cancer or OligomEts

ABSTRACT

Introduction: The COVID-19 pandemic led to worldwide barriers to access to operating rooms;some multidisciplinary thoracic oncology teams pivoted to a paradigm of stereotactic ablative radiotherapy (SABR) as a bridge to provide radical-intent treatment combining immediate SABR followed by planned surgery when surgical resource constraints ameliorated. This pragmatic approach, termed SABR-BRIDGE, was instituted with prospective data collection at four institutions (3 Canada, 1 USA);herein we present the surgical and pathological results from this approach. Methods: Eligible participants had early-stage presumed or biopsy-proven lung malignancy that would otherwise be surgically-resected. SABR was delivered using standard institutional guidelines with one of three fractionation regimens 30-34 Gy /1 fraction, 45-55 Gy/3-5 fractions, or 60 Gy/8 fractions. Surgery was recommended at a minimum of 3 months following SABR with standardized pathologic assessment of resected tissue. A pathological complete response (pCR) was defined as absence of viable cancer, and a major pathologic response (MPR) was defined as ≤10% viable tissue. Results: Seventy-five participants were enrolled, of which 72 received SABR. Following SABR, 26 patients underwent resection, while 46 did not;reasons for not undergoing surgery included metastasis (n=2), non-cancer death (n=1), awaiting lung surgery (n=13) and patient choice given favorable post-SABR imaging response (n=30). Of 26 patients who underwent resection, 62% had a pre-treatment biopsy. The most common SABR regimens were 34 Gy /1 fraction (31%) and 48 Gy in 3-4 fractions (31%). SABR was well-tolerated, with two grade 1 toxicities (pain, 7.7%), and one grade 3 pneumonitis (3.8%). Median time-to-surgery was 4.5 months from SABR completion (range2-17.5 months). Most had minimally-invasive surgery (n=19, 73%) with 4 patients (15%) requiring conversion to thoracotomy, and 3 (12%) had planned open operation. Surgery was reported as being more difficult because of SABR in 38% (n=10). There were two intraoperative complications (7.7%, pulmonary artery injury), and 8 patients with post-operative complications (31%, all grade 2, most commonly air leaks [n=5]). The amount of residual primary tumor ranged from 0% to 90%. Thirteen (50%) had pCR while 19 (73%) had MPR. Rates of pCR were higher in patients operated upon at earlier time points (75% if within 3 months, 50% if 3-6 months, and 33% if ≥6 months). Rates of pCR were higher in patients without pre-treatment tissue diagnosis (91% versus 20% in those without and with tissue diagnosis, respectively). In 31% (n=8) of patients, nodal disease was discovered on resection, with half being N2 (4/26=15%). Conclusions: The SABR-BRIDGE approach allowed for delivery of treatment with minimal upstaging during a period of operating room closure & high risk for patients. Surgery was well-tolerated. However, most patients who received SABR did not proceed to surgery, limiting precise estimates of pCR rates. However, the reported pCR rate is consistent with previous phase II trial data. Keywords lung surgery, SBRT, Multi-modal therapy