Stereotactic Body Radiation Therapy: A New Paradigm for Radiation Treatment in Lung Cancer
Randomized Data Confirms the Long-Term Effectiveness of SBRT for Lung Cancer
While surgery is the standard treatment for stage 1 non-small-cell lung cancer (NSCLC), patients who are not candidates for surgery have traditionally turned to conventionally fractionated radiotherapy as a potential treatment or cure.
But there have been drawbacks. To be effective in targeting tumors, radiotherapy requires high doses of radiation to destroy cancer cells, and in the process, may damage healthy cells and tissues near the treatment area. In addition, daily conventional radiation therapy for NSCLC could extend to six or more weeks of treatment.
However, as technology has advanced, new technology with superior image guidance and tumor motion management has emerged — stereotactic body radiotherapy therapy (SBRT) or stereotactic ablative body radiotherapy (SABR) — which allows for more precise delivery of high radiation dose to the tumor over a substantially shorter period of time with less damage to surrounding healthy tissues.
“In the setting in which a smaller tumor is physically or geographically amenable, the daily radiation dose can be much higher which allows for a shorter course of treatment for the patient, which can be as few as one, but is often in the range of 3-5 fractions,” said Daniel A. Hamstra, MD, PhD, clinical director at Beaumont Health, Dearborn, MI.
In the past two decades, SBRT/SABR has rapidly emerged as an effective and safe treatment for early-stage inoperable NSCLC and is now the standard of care for inoperable patients as described in multiple evidence-based guidelines.
Nevertheless, direct comparisons to conventionally fractionated radiotherapy to assess the effectiveness of SBRT/SABR for NSCLC have been relatively limited, said Dr. Hamstra, a member of the RSNA Oncologic Imaging and Therapies Task Force under the RSNA News Editorial Board.
“Initial trials were promising and were then followed by a landmark phase II cooperative group trial — RTOG 0236,” said Drew Moghanaki, MD, MPH, chief of radiation oncology, Atlanta VA Health Care System, and acting associate professor, Emory Winship Cancer Institute, Atlanta. “The results confirmed a previously serendipitous finding of 93% tumor control in the primary tumor with an overall survival rate of 40% after five years of follow-up in inoperable patients.”
But questions remained about these findings, primarily because the study did not use a control arm comparing SBRT to conventional radiotherapy. For this reason, clinical investigators were left to wonder whether the outcomes in the RTOG 0236 study may have been the result of patient selection versus the dose/fractionation prescription
Research Focuses on Phase 3 Trials
In February 2019, a study in The Lancet by Emeritus Prof. David Ball, MD, of the Peter MacCallum Cancer Centre, Melbourne, VIC, and colleagues, reported the results of the first Phase III randomized trial that compared SABR with conventionally fractionated radiotherapy in patients with inoperable peripherally located stage 1 NSCLC.
- 101 eligible patients were randomly assigned to receive SABR (n=66) or standard radiotherapy (n=35) between Dec. 31, 2009, and June 22, 2015.
- Research was conducted in 11 hospitals in Australia and three hospitals in New Zealand.
- As of July 31, 2017, median follow-up for local treatment failure was 2.1 years (interquartile range [IQR] 1.2–3.6) for patients randomly assigned to standard radiotherapy and 2.6 years (IQR 1.6–3.6) for patients assigned to SABR.
- 20% of 101 patients had progressed locally (nine [14%] of 66 patients in the SABR group and 11 [31%] of 35 patients in the standard radiotherapy group).
- Freedom from local treatment failure was improved in the SABR group compared with the standard radiotherapy group (hazard ratio 0.32, 95% CI 0.13–0.77, p=0.0077)
- Median time to local treatment failure was not reached in either group.
- Similarly, the overall survival for patients assigned to SABR was longer than with standard radiotherapy.
- Median overall survival was 5 years (95% CI 3.4 to not estimable) in the SABR group and 3 years (1.9 to not estimable) in the standard radiotherapy group (HR 0.53 [95% CI 0.30–0.94], p=0.027; figure 3).
- Overall survival at 2 years was 77% (95% CI 67–88) for those in the SABR group and 59% (44–78) for those in the standard radiotherapy group.
“To our knowledge, this was the first randomized trial to compare stereotactic ablative body radiotherapy with standard radiotherapy in patients who had pathologically proven non-small cell lung cancer at Stage 1,” said lead author David Ball, MD, deputy director of Radiation Oncology & Cancer Imaging and chair of Lung Service, Peter MacCallum Cancer Centre, Melbourne, Australia.
Researchers say the results open the door for expanded use of SBRT/SABR in patients with NSCLC.
For more information about managing high-risk radiologic features with SABR and the future of SBRT/SABR, read the September issue of RSNA News.
For More Information
Access the 2014 study, “Long-term Results of RTOG 0236: A Phase II Trial of Stereotactic Body Radiation Therapy (SBRT) in the Treatment of Patients with Medically Inoperable Stage I Non-Small Cell Lung Cancer,” by Robert Timmerman, MD, and colleagues, at redjournal.org.
Access the 2018 study, “Stereotactic Ablative radiotherapy versus standard radiotherapy in stage 1 non-small-cell lung cancer (TROG 09.02 CHISEL): A phase 3, open-label, randomized controlled trial,” by David Ball, MD, and colleagues at thelancet.com.
Guidelines for Managing Early-Stage Non-small Cell Lung Cancer After SABR
The 2018 study, “Optimal Imaging Surveillance After Stereotactic Ablative Radiation Therapy for Early-Stage Non-Small Cell Lung Cancer: Findings of an International Delphi Consensus Study,” in Practical Radiation Oncology, provides international expert consensus on areas of uncertainty in the management of early-stage non-small cell lung cancer patients after SABR, including:
Chest CT Scans Should be Ordered Routinely in Follow-Up
- If there is suspicion for local recurrence (LR), FDG-PET/CT scans are strongly recommended;
- CT is recommended at three, six and 12 months in the first year, every six months in the second year of follow-up, and annually up to five years;
- After five years, chest CT should continue, although no consensus was reached regarding frequency.
Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
Guidelines suggest that current RECIST criteria is not sufficient for detecting LR. Instead:
- A formal scoring system, informed by validated data, should be used to classify high-risk imaging features predictive of LR;
- CT findings suspicious for LR include infiltration into adjacent structures, bulging margins, sustained growth, mass-like growth, spherical growth, craniocaudal growth and loss of air bronchograms.
- May be considered without pathologic confirmation of recurrence if imaging findings are highly suspicious and a biopsy is not safe/feasible, or if an attempted biopsy was nondiagnostic. Access the study at practicalradonc.org.