Impact of Stereotactic Ablative Radiotherapy on Survival for Patients With Advanced Cancers
The first report from a phase II, multicenter clinical trial has found that a newer, more aggressive form of radiation therapy—stereotactic ablative radiation—can extend long-term survival for some patients with stage IV cancers, while maintaining their quality of life. The study was published by Sutera et al in the International Journal of Radiation Oncology • Biology • Physics.
“Despite many advances in cancer care over the past 20 to 30 years, some patients still go on to develop metastatic, or stage IV, disease. Generally speaking, radiation therapy in that setting has been used only to make the patient comfortable,” said senior study author Dwight E. Heron, MD, MBA, FACRO, FACR, Director of Radiation Services at UPMC Hillman Cancer Center. “It also has been the case, however, that a small number of patients with stage IV disease could have surgery to remove their metastases and live a long time. And so our question was, could we use highly focused radiation to destroy those tumors and have the same effect as surgery? The initial answer from this large prospective trial is yes.”
Patients in the trial were treated with stereotactic ablative radiation therapy. Increasing evidence points to stereotactic ablative radiotherapy as a viable alternative when patients cannot undergo surgery to remove metastatic tumors.
“With stereotactic radiation, we use a different type of highly precise local therapy to target tumors in the lungs, liver, bones, or kidneys with precision that is analogous to surgery, and with very few side effects or harm to the patient's quality of life,” said Dr. Heron, who is also a Professor of Radiation Oncology, Otolaryngology, and Head and Neck Surgery at the University of Pittsburgh School of Medicine.
Study Methods
In this phase II trial, Dr. Heron and his colleagues enrolled 147 patients across 3 large cancer centers to evaluate the safety and feasibility of stereotactic ablative radiation for a variety of oligometastatic cancers. Each patient had up to 5 metastases—most had either 1 (71%) or 2 (19%)—in 1 to 3 new sites. The metastases were located most commonly in the lung (52%), followed by lymph nodes (16.5%), bone (15%), or liver (7%).
All patients received stereotactic radiation to all metastatic sites. Radiation dosing and fractionation were dependent on the size and location of each metastasis. All patients had good performance status (ECOG 0–1) and a life expectancy of more than 6 months. Median follow-up time for this report was 41.3 months (range = 14.6–59.0).
Findings
Following treatment with stereotactic radiation, more than 8 in 10 patients (84%) survived at least 1 year, and 4 in 10 (43%) survived 5 years or longer. The median overall survival was 42.3 months.
Local recurrences were uncommon; half of the patients experienced complete (26%) or partial (26%) remission following treatment. An additional third (32%) had stable disease. The remaining patients either had local progression following treatment (14%) or their response could not be determined (12%).
Distant recurrences were more common, with a median time of 8.7 months until distant progression. The 1-year and 5-year rates of distant progression–free survival were 44% and 17%, respectively.
The type of primary tumor was associated with both overall survival (P = .002) and distant progression–free survival (P = .008). Patients with primary breast (9%), prostate (7.5%), and colorectal (21%) tumors had longer survival than those with primary lung (22%) or head and neck (11%) tumors.
Severe side effects were limited—just under 10% of patients experienced short-term toxicity of grade 2 or higher, including one grade 3 case each of labored breathing, skin inflammation, and anemia. Even fewer patients had severe long-term toxicity, with one grade 3 ureter obstruction and one grade 4 obstruction of the small bowel.
Patient-Reported Quality of Life
A unique aspect of the trial design was the decision to use patient-reported rather than physician-assessed quality of life. Patients reported no significant changes in their quality of life immediately after completing stereotactic radiation, nor at 6 weeks, 3 months, and 9 months of follow-up. At the 6- and 12-month marks, quality of life was significantly better than before treatment.
“Many of the cancer treatments we deliver, even though they have a therapeutic benefit, also are associated with some toxicity, and that may impact patients’ quality of life. In this study, for patients with stage IV disease, we have a treatment paradigm that can result in long-term survival while maintaining overall quality of life. We had a sense this was the case from retrospective data, but the addition of prospective data is very convincing,” said Dr. Heron.
Dr. Heron said his team plans to continue enrolling patients into the trial, with a goal of expanding the current 147 patients to roughly 200 total patients. Moving forward with additional trials, they also will look at treating patients with larger numbers of metastatic lesions and combining stereotactic radiation with emerging treatments such as immunotherapy.
“In combination with immunotherapy, stereotactic radiation therapy may set a new bar for achieving better outcomes, lowering side effects, and improving our patients’ quality of life,” concluded Dr. Heron.
Disclosure: The study authors' full disclosures can be found at redjournal.org.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
