Clinical Investigation
Initial Results of a Multicenter Phase 2 Trial of Stereotactic Ablative Radiation Therapy for Oligometastatic Cancer

https://doi.org/10.1016/j.ijrobp.2018.08.027Get rights and content

Purpose

Oligometastatic disease has emerged as a potentially curable state in the spectrum of cancer progression. Aggressive local therapy such as stereotactic ablative radiation therapy (SABR) may improve oncologic outcomes. Herein, we report the initial oncologic outcomes and patient-reported quality of life (PR-QoL) from a phase 2 multicenter trial for patients with oliogmetastatic disease.

Methods and Materials

Patients with oligometastatic disease (1-5 metastases) were prospectively recruited between 2011 and 2017. SABR dose and fractionation was dependent on the lesion size and location. Patient follow-up occurred within 6 weeks of completion of SABR and at 3-month intervals. Patients received a Functional Assessment of Cancer Therapy-General questionnaire at baseline and at each follow-up to assess for PR-QoL. Median follow-up was calculated by reverse Kaplan-Meier method. Overall survival (OS), local progression-free survival, and distant progression-free survival were calculated using the Kaplan-Meier method.

Results

We enrolled 147 patients with oligometastatic cancer with a median age of 66.4 years (interquartile range, 59.9-74.6). The most common primary tumors included lung (21.8%, non-small cell: n = 29, small cell: n = 3), colorectal adenocarcinoma (21.1%), and head and neck (10.9%, squamous cell carcinoma: n = 11). In a median follow-up of 41.3 months (interquartile range: 14.6-59.0), the median OS was 42.3 months (95% confidence interval: 27.4-∞) with 5-year OS of 43%. Five-year local progression-free survival and distant progression-free survival were 74% and 17%, respectively. Acute grade 2+ and 3+ toxicity were 7.5% and 2.0%, respectively, and late grade 2+ and 3+ toxicity were both 1.4%. There was no significant change in quality of life at completion and 6 weeks, 3 months, and 9 months after treatment. At 6 and 12 months, patients were found to have statistically significant improvement in PR-QoL.

Conclusions

This multicenter prospective phase 2 study demonstrates that SABR for recurrent oligometastatic cancer is a feasible and tolerable treatment option with minimal acute and late grade 3 toxicity. Additionally, PR-QoL was not adversely affected.

Introduction

Metastatic cancer has a notoriously poor prognosis, with 5-year survival ranging from 4% to 38% based on tumor location and histology.1 Numerous reports have identified a subset of patients with a limited volume of metastatic disease, termed oligometastatic, who may respond well to aggressive local therapy.2, 3, 4 Because oligometastatic disease has not yet experienced widespread tumor cell dissociation, the sites of tumor burden are limited.5 Aggressive treatment to oligometastatic disease sites could, therefore, decrease tumor burden and provide long-term disease control. Surgical series have demonstrated survival benefits to this approach in numerous cancer types.6, 7, 8, 9 Stereotactic ablative radiation therapy (SABR) consists of high-dose radiation delivered in a highly precise manner.10 SABR allows for excellent local control and limited radiation to surrounding normal tissue. SABR is well tolerated and thus can be performed in patients who are not fit for surgery. Herein we report patient outcomes, toxicity, and quality of life of patients with oligometastatic cancer prospectively treated with SABR.

Section snippets

Patient selection

This was a multicenter prospective phase 2 study evaluating the safety and feasibility of SABR for patients with oligometastatic cancer. Patients included in this analysis were aged ≥18 years and had biopsy-proven oligometastatic or recurrent cancer. Oligometastatic disease was defined as 5 or fewer total sites of metastases in 3 or fewer organs on fluorodeoxyglucose positron emission tomography/computed tomography (CT) scan within 8 weeks of enrollment. Additional eligibility criteria included

Patient and treatment characteristics

From 2011 to 2017, 147 patients were enrolled. The median age at enrollment was 66.4 years (interquartile range, 59.9-74.6) with 51.0% being female. The most common primary tumors included lung (21.8%; non-small cell lung cancer: n = 29; small cell lung cancer: n = 3), colorectal adenocarcinoma (21.1%), head and neck (10.9%, squamous cell carcinoma: n = 11), breast carcinoma (8.8%), and prostate adenocarcinoma (7.5%). The primary lung tumor was treated with a combination of surgery (73.5%),

Discussion

This prospective phase 2 trial investigated the safety and efficacy of SABR for oligometastatic cancer. The oligometastatic state is hypothesized as an interim stage of systemic disease, with a higher potential for durable disease control after aggressive local treatments.2, 4 SABR has generated significant interest in providing localized treatment of oligometastatic lesions. Herein we show SABR to be a safe treatment modality with excellent local control and OS for patients with

Conclusions

This multicenter prospective phase 2 study demonstrates the feasibility and safety of SABR for oligometastatic cancer. This treatment regimen was well tolerated with limited grade 3+ acute and late toxicity and no significant adverse effect on quality of life. Our results demonstrate excellent long-term survival and local control of metastatic sites. Future randomized controlled trials will be needed to definitively determine the role of aggressive local therapy for oligometastatic disease.

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