Stereotactic body radiation therapy for lung, spine and oligometastatic disease: current evidence and future directions

Abstract

Stereotactic body radiation therapy (SBRT) also referred to as stereotactic ablative radiotherapy (SABR), is a technique which has emerged over the past two decades due to improvements in radiation technology. Unlike conventional external beam radiotherapy (cEBRT) which traditionally delivers radiation in small doses [approximately 2 Gray (Gy) per fraction] over several weeks, SBRT, typically delivered in one to eight fractions, is a technique whereby potentially ablative doses of radiotherapy (usually 7.5-20 Gy per fraction) can be delivered with steeper dose gradients and sub millimetre precision, minimising risk to surrounding normal tissues. The potential benefits of excellent tumor control with low toxicity has led to the increasing use of SBRT in a number of clinical situations. Due to compelling evidence, SBRT is now the treatment of choice for medically inoperable patients with peripherally located stage I non-small cell lung cancer (NSCLC). Controversy remains however as to its efficacy and safety for central or ultra-central lung tumors. The evidence base supporting the use of SBRT as a novel treatment for spinal metastases and oligometastases is rapidly expanding but challenges remain in these difficult patient populations. In an era where targeted therapy and improved systemic treatments for stage IV cancer have resulted in increased disease-free survival, and our knowledge of the oligometastatic state is ever expanding, using SBRT to treat metastatic disease and gain durable local control is increasingly desirable. Several randomized trials are currently underway and are sure to provide valuable information on the benefit and utility of SBRT across many tumor sites including early-stage NSCLC, spinal metastases and oligometastatic disease. Recognizing the evolving role of SBRT in clinical practice, this paper provides a critical review of recent developments in each of these areas particularly highlighting the challenges facing clinicians and discusses potential areas for future research.

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

“…With more advanced 4D imaging techniques, motion management, conformal treatment planning, and daily imaging guidance, SBRT is able to deliver high doses in few fractions in a highly conformal fashion providing a steep dose fall‐off outside the target . In the medically inoperable early‐stage NSCLC setting, SBRT achieves local control rates of ~90% at 3–5 yr and overall survival (OS) of 55%–60% at 3 yr and has been established as a safe and effective alternative treatment option for this group of patients . However, due to excellent local control rates, low toxicity and the noninvasive delivery of SBRT, there has been an increased use of SBRT in early‐stage NSCLC patients who are candidates for surgery.…”

“…While tumors located in the periphery of the lung can tolerate single fraction or 3‐fraction SBRT, it is not safe to treat tumors located more centrally and close to critical organs at risk (OARs), such as the heart, major vessels and proximal airways. This brings us to the next issue with the word “all” in this statement, as delivering high single doses of radiation to central tumors (within 2 cm of the tracheobronchial tree) even with the most highly conformal technology can result in excessive toxicity, especially if the treatment is delivered in ≤3 fractions . To mitigate toxicity, “risk‐adapted” SBRT regimes of 4–8 fractions are now being used to treat central tumors .…”

“…This brings us to the next issue with the word “all” in this statement, as delivering high single doses of radiation to central tumors (within 2 cm of the tracheobronchial tree) even with the most highly conformal technology can result in excessive toxicity, especially if the treatment is delivered in ≤3 fractions . To mitigate toxicity, “risk‐adapted” SBRT regimes of 4–8 fractions are now being used to treat central tumors . However, SBRT is still not recommended for “ultra‐central” lung tumors which directly touch major airways and more conventional schedules (with lower biological equivalent dose (BED) and hence lower control rate) are recommended .…”

“…To mitigate toxicity, “risk‐adapted” SBRT regimes of 4–8 fractions are now being used to treat central tumors . However, SBRT is still not recommended for “ultra‐central” lung tumors which directly touch major airways and more conventional schedules (with lower biological equivalent dose (BED) and hence lower control rate) are recommended . Patients with centrally located tumors remain a therapeutic challenge for both surgery and radiotherapy.…”

“…However, studies to date suggest that hypofractionation with high doses as used for SBRT may worsen hypoxia in tumors, including NCSLC and result in reduced cell kill. The different biological response of tumors treated with hypofractionation of larger doses compared to conventional regimens may have resulted in the uncertainty that exists on the optimal prescription dose and number of treatment fractions that should be used for treating early‐stage NSCLC with SBRT . As Ruggieri et al.…”