Stereotactic body radiation therapy for oligometastatic pulmonary tumors from cervical cancer

Abstract Objective To evaluate the efficacy and toxicity of stereotactic body radiation therapy (SBRT) for oligometastatic pulmonary tumors from cervical cancer. Methods A total of 29 oligometastatic pulmonary lesions from cervical cancer in 19 patients were treated with SBRT in our institute from 2011 to 2016. Thirteen patients (68.4%) suffered with solitary lung metastasis, three patients (15.8%) with multiple unilateral lesions and three patients (15.8%) with bilateral lesions. The median size of lung lesions was 2 cm (0.7–5.6 cm). Patients underwent cone‐beam CT before the delivery of SBRT. The most common dose fractionation schemes were 64 Gy in eight fractions (eight lesions) and 56 Gy in seven fractions (seven lesions). Nine patients (47.4%) received systemic chemotherapy. Results The median follow‐up was 9.5 months (3.0–62.4 months). The one‐year overall survival (OS), progression‐free survival (PFS) and local control (LC) rates were 76.8%, 55.8% and 75.6%, respectively. The median PFS was 12.7 months. Six patients (31.6%) gained more than 20 months disease‐free survival. Eleven patients (57.9%) experienced tumor relapse, including seven patients with pulmonary relapse and four patients with extra‐pulmonary disease. Only one patient (5.3%) experienced symptomatic radiation pneumonitis (grade 2). Conclusion SBRT was an efficacy and safe approach for patients with oligometastatic pulmonary tumor from cervical cancer. SBRT should be considered as a potential alternative to resection for these patients.


INTRODUCTION
Cervical cancer is one of the most common cancers in China. It was estimated that there were 98.9 thousand new cervical cancer cases and 30.5 thousands deaths in 2015. 1 With the changes of treatment pattern and development of treatment technique, the local control (LC) of cervical cancer improved significantly. After definitive treatment, there was more distant failure than local failure. 2,3 Pulmonary metastasis is one of the most common sites of distant failure. It was reported that the incidences of pulmonary metastasis were 1.8-2.1%. 4,5 For pulmonary metastases from cervical cancer after initial treatment (radical surgery or definitive radiotherapy), pulmonary resection This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. is an efficacy approach, with a 5-year survival of more than 30%. 6,7 However, only patients with few metastatic lesions limited to the lungs and good general condition could receive pulmonary resection and only a small number of patients meets these criteria. Most patients with pulmonary metastases from cervical cancer were treated with chemotherapy or radiotherapy. As a palliative treatment, the survival after single chemotherapy was poor. Panek  have long-term survival. Therefore, just giving these patients single chemotherapy is unreasonable.
In the past, radiotherapy was often used as a palliative approach for pulmonary metastases. As a new technique, stereotactic body radiation therapy (SBRT) could accurately deliver high dose to the lesions in few fractions. In pulmonary metastasis from rectum and soft tissue sarcoma, SBRT had been proved to be a safe and effective approach 9-11 and became an important alternative to resection.
For the use of SBRT in pulmonary metastases from cervical cancer, researches are limited. In this article, we retrospectively analyzed the efficacy and toxicity of SBRT for patients with pulmonary metastases from cervical cancer after definitive treatment in our institute.

Patients
We retrospectively analyzed patients with pulmonary metastases from cervical cancer treated with SBRT from January 2011 to July

Treatment
A CT simulation was performed with 16-slice Philips Brilliance Big Bore  Table 1.

Outcome evaluation and statistical analysis
Response Evaluation Criteria in Solid Tumors criteria was used to assess the treatment efficacy. Treatment-related adverse effects were graded according to Common Terminology Criteria for Adverse Effects

RESULTS
The median follow-up was 9.5 months (range, 3.0-62.4  patients with pulmonary metastases from cervical cancer with surgical resection, the 5-year OS was 45.7%. 7 For patients with pulmonary metastases from cervical cancer after radical treatment, surgical resection is an efficacy approach. The 5-year survival was higher than 30%.
For patients with pulmonary metastases, SBRT was an effective treatment option. The 2 or 3-year LC rate was higher than 70%. [9][10][11] In the pooled analysis of Germen working group, 700 patients with medically inoperable lung metastases in 20 centers were treated with SBRT.
The median diameter of the lesions was 2.2 cm (range 0.4-9.4 cm).
The median single fraction dose of PTV was 12.5 Gy (range 3-33 Gy) and the median number of SBRT fractions was 3 (range, 1-13 in a median number of three fractions (range 1-13). 9 The radiation sensitivity of lung metastases varies with different primary tumors.
The radiation sensitivity of cervical cancer was comparatively higher than sarcoma, colorectal cancer, renal cell carcinoma and NSCLC et al.
In this study, the most common dose fractionations were 64 Gy in 8 fractions (8 lesions), 56 Gy in 7 fractions (7 lesions). The median BED was 100.8 Gy (56-120 Gy). With these dose fractionations, SBRT achieved excellent LC and promising OS. This may provide an acceptable dose fractionation option for pulmonary metastases from cervical cancer.
It was reported that the incidence rates of grade 2 or greater radiation pneumonitis were 0-6.5% for patients with pulmonary metastases when they treated with SBRT. [9][10][11]15,16 In this study, only 1 (5.3%) patients had grade 2 radiation pneumonitis, which was similar with previous reports.
There were some limitations in this study. The number of patients with pulmonary metastases from cervical cancer was small and the follow-up period was short. As pulmonary metastases from cervical cancer are comparatively rare, 4 multi-institute studies are needed to collect more patients in the future.
SBRT was an efficacy and safe approach for patents with oligometastatic pulmonary tumor from cervical cancer. SBRT should be considered as a potential alternative to resection for these patients.

CONFLICTS OF INTEREST
The authors declare that they have no conflict of interest.