In cancer patients with oligometastases, stereotactic body radiotherapy (SBRT) in doses developed for single metastasis or primary tumors is safe, causing no treatment-related deaths, according to results from the phase I National Cancer Institute trial NRG-BR001 trial published in JAMA Oncology. In these patients, however, late grade 3 adverse events (AE) warrant extended follow-up.
Researchers led by Steve Chmura, MD, of the University of Chicago, explained the difficulties in treating patients with three to four metastases or those with two metastases in close proximity.
“Delivering SBRT to patients with 3 to 4 metastases or those with 2 metastases in close proximity to one another is technically challenging. As the number of metastases treated increases, the cumulative radiation dose to the surrounding organs increases the potential for treatment-related toxicity. Additionally, this challenge is magnified, because many patients with oligometastases have had prior radiotherapy, limiting further permissible dose to surrounding normal tissue,” they wrote.
From a consortium of North American academic and community practice cancer centers that participated in NRG Oncology trials, Chmura et al included 35 patients (mean age: 63.1 years; 57.1% men; 85.7% White) with breast (34.3%), prostate (37.1%), or non-small cell lung cancer (28.6%) who had three to four metastases or two metastases that were in close proximity. The median number of metastases per patient was three.
Included patients had metastases in seven locations, including bone/osseous (B), spinal/paraspinal (SP), peripheral lung (PL), central lung (CL), abdominal-pelvic (AP), mediastinal/cervical lymph node (MC), and liver (L).
The primary end point of the study was dose-limiting toxicity (DLT) as defined by the Common Terminology Criteria for Adverse Events (version 4.0), as specific adverse events (AEs) of grades 3 to 5 related to SBRT within 180 days of treatments. Researchers classified dose levels as safe if DLTs occurred in no more than one of six patients per location.
Patients underwent planning CT, after which each metastasis was targeted. For all but spinal metastases, an additional 5- to 7-mm expansion was included for setup uncertainty. Median follow-up was 22.6 months. SBRT was initiated at a dose of 50 GY in five fractions for patients with CL and MC; 45 Gy in three fractions for those with PL, AP, and L; and 30 Gy in three fractions for those with BO and SP.
Standard doses were safe in all 35 evaluable patients, and there were no protocol-defined dose-limiting toxicities. Of the 50 grade 3 to 4 AEs that occurred in 18 patients, 18 (36%, in nine patients) were reported to be at least possibly related to therapy. Six of these occurred within 180 days. None of these AEs met the defined criteria for DLT.
Median survival was not reached, and no protocol defined DLTs occurred. Estimated two-year overall survival was 57%.
“These dosing schemes are important, as the use of SBRT to treat multiple metastases is increasing with mounting randomized evidence. These recommended doses from NRG-BR001 are being used in ongoing trials, including NRG-BR002, the phase 2R/3 trial to determine the role of this treatment for patients with metastatic breast cancer,” concluded Chmura and fellow researchers.
In an accompanying editorial, Charles R. Thomas, Jr., MD, of the Oregon Health Sciences University, Portland, and Deputy Editor of JAMA Oncology, commended these researchers, and noted that their results “provide evidence to guide patient care and serves as a framework in the development of next-generation, multi-institution, SBRT-based clinical trials for patients with oligometastatic disease.”
Thomas added a caveat, however, to his summation: “[S]ince the trial was activated, multiple systemic agents have been approved for patients with advanced lung, breast, and prostate cancer. Consequently, many of these patients may live long enough to eventually manifest radiation-induced normal tissue toxicity. Because these toxic effects, particularly bone fractions and pulmonary toxicity, can compromise daily quality of life, we strongly believe that clinicians must be sure to caution patients about the specific normal tissue toxicity profile that can occur depending on the anatomic site that is to be targeted with SBRT,” concluded Thomas.
Limitations of the study include that it was a phase I trial, and although no dose reductions were necessary, if treatment were given on a wider scale, toxicity rates may be higher.
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Standard ablative radiation schedules appear to be safe for patients with oligometastatic disease with three to four metastases or two metastases in close proximity to each other.
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In this National Cancer Institute–sponsored phase I trial, 35 patients with oligometastatic breast, prostate, or non–small cell lung cancer were treated with ablative radiation, and standard doses were found to be safe in all.
Liz Meszaros, Deputy Managing Editor, BreakingMED™
This study was supported by grant UG1CA189867 (NRG Oncology NCORP), U10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology Statistics and Data Management Center; Ms Winter and Ms Moughan), and U24CA180803 (IROC) from the NCI.
Chmura and Thomas reported no disclosures.
Cat ID: 482
Topic ID: 95,482,730,22,24,25,935,192,925,482
