Operable Stage I Non-Small Cell Lung Cancer Treated with Stereotactic Radiotherapy (SBRT) Compared to Surgical Lobectomy: Failure Patterns and Implications for Management

Abstract

Purpose/Objective(s): For NSCLC patients treated with SBRT, we investigated if proximity to the proximal bronchial tree is associated with non-cancer death. Materials/Methods: From 2006-2013 patients with a single early stage NSCLC tumors were irradiated with CBCT guided SBRT (median dose 54 Gy in 3 fractions) in 5 institutes. Patients with progressive disease, metastases, or second cancers at the time of death were scored as death from cancer; all other deceased patients were scored as non-cancer death. Treatment plans were collected, and the main and lobar bronchi were automatically delineated using atlas based segmentation. For each patient the shortest distance from the edge of the GTV to the proximal bronchial tree (PBT) was determined. Patients were stratified into 3 groups; GTV2 cm from the PBT (peripheral (A); RTOG 0236), GTV 1 cm and < 2 cm from the PBT (B), and GTV <1 cm from the PBT (C). Actuarial non-cancer survival at 1y, 2y and 5y were determined (i.e., death from cancer was censored). Association between the stratified distance of the GTV to the PBT and non-cancer death were evaluated using univariate Cox regression (at the P<0.05 level), and compared to the association with cause specific survival to test for competing mortality risk. Finally, the stratified distance was included in a multivariate Cox analysis, also including; age, gender, performance status, comorbidity index, lung-function FEV1, Mean Lung Dose, tumor diameter, and smoking history. Results: Seven hundred sixty-nine patients were identified with a median age of 75 y. Median Biologically Equivalent Dose (a/b Z 10 Gy) was 126 Gy, 180 Gy and 227 Gy for group C, B, and A, respectively, with 33, 71 and 665 patients per group. Median GTV diameter was 4.1 cm (1.1-7.0), 2.7 cm (0.9-5.7) and 2.2 cm (0.7-6.5) for groups C, B, and A, respectively. Survival rates were lower for patients in group C (Table 1) with a Hazard ratio (HR) of 2.91 (P < 0.001). Patients in group B had a lower, non-significant HR of 0.87 (P Z 0.554). The association with cause specific survival showed a significantly higher HR (2.45, P Z 0.036) for patients in group C with respect to A, but not B. In the multivariate Cox analysis, the stratified distance from the GTV to PBT was significantly associated with non-cancer death (group C: P<0.001, HR Z 3.56, group B: P Z 0.319, HR Z 0.79), as well as age (P Z 0.001, HR Z 1.03), performance status (P<0.001, HR Z 0.30) and lung-function FEV1 (P Z 0.004, HR Z 0.99). Conclusion: Patients with a tumor < 1 cm from the proximal bronchial tree had 3.56 fold higher risk of non-cancer death than patients with a peripheral tumor. Delivered dose distributions will be further studied.

Stereotactic body radiation therapy (SBRT) for early stage non-small cell lung cancer (NSCLC): contemporary insights and advances

“…This is in contrast to a Dutch propensity-matched analysis of 64 SABR and 64 video-assisted thoracoscopic surgery (VATS) lobectomy patients, which showed superior 3-year locoregional control with SABR (93.3% vs. 82.6%) with no difference in distant recurrence or OS (87). Contrarily, recent data from a single institution shows higher rates of regional and clinical failure in SBRT compared to lobectomy with lower disease-free and OS, despite similar rates of local recurrence and distant metastasis (88).…”

“…However, recent evidence suggests heterogeneity in tumor response depends on tumor subtype. Recent studies have shown a significantly higher local failure rate for squamous cell cancers over adenocarcinomas as well as other NSCLCs (88,110,111). Another study showed that heterogeneity exists even within adenocarcinomas, with micropapillary and solid subtypes correlating with higher rates of locoregional and distant failure (112).…”

Three discipline collaborative radiation therapy (3DCRT) special debate: I would treat all early‐stage NSCLC patients with SBRT

“…One limitation of SBRT is the lack of formal surgical nodal staging which results in inclusion of patients with micrometastatic disease, resulting in higher rates of regional recurrence in comparison to surgery . Use of modern endobronchial ultrasound and PET‐CT‐based staging may reduce this disparity.…”