Abstract
Splenic metastases from oligometastatic ovarian carcinoma are a rare occurrence. Usual treatment for splenic metastases includes splenectomy, but some patients are either unable or unwilling to undergo surgery. Stereotactic body radiotherapy (SBRT) is an effective ablative modality for treating metastatic disease. SBRT to abdominopelvic tumors has been shown to be safe and effective for properly-selected patients and is particularly attractive in the oligometastatic setting as an alternative to radical resection. In this case study, we report a patient with an isolated splenic metastasis from ovarian carcinoma treated with 50 Gy in 10 fractions.
Keywords: spleen metastasis, isolated splenic metastasis, ovarian carcinoma, stereotactic body radiotherapy
Introduction
Oligometastatic disease may represent a potentially curable intermediate state of disease in metastatic patients. Initial experiences relied upon surgical resection of metastatic lesions but ablative radiation therapy techniques are becoming increasingly commonplace. More recently, clinical trials have demonstrated the utility of stereotactic body radiotherapy (SBRT) in the management of patients with oligometastatic disease from various primary sites, particularly in the setting of limited oligometastatic disease [1-4].
Splenic metastases are rare, occurring in 7% of patients in autopsy series, most frequently in breast, lung, melanoma, and gynecologic malignancies [5-7]. Splenectomy may be a component of cytoreduction for patients with ovarian carcinoma involving the spleen undergoing radical resection. Few data exist with regard to the utilization of non-surgical local therapies. We present a case of an 85-year-old female with a splenic metastasis of ovarian carcinoma who underwent SBRT to the spleen for definitive treatment.
Clinical Case
An 85-year-old female was diagnosed with ovarian epithelial carcinoma after presenting with an abdominopelvic mass and serum cancer antigen 125 (CA-125) of 98.8 U/ml (reference range, 0-20.9). Initial therapy included cytoreductive surgery; pathology revealed high-grade serous adenocarcinoma of the ovary. She was treated with adjuvant and intraperitoneal chemotherapy and bevacizumab on clinical trial (NCT00951496).
Forty-two months after completion of therapy, she developed a solitary 1.9 cm hypoenhancing lesion in the spleen that enlarged with serial scans with increase in CA-125 from 16.04 to 36.39. She received 4 months of liposomal doxorubicin and carboplatin followed by 7 months of aromatase inhibition until progression of the still-isolated spleen metastasis. She declined surgical resection and was referred to radiation oncology. She was counseled regarding functional asplenia after treatment and was vaccinated against encapsulated organisms. The patient was treated with SBRT over the course of 2 weeks (Figure 1A).
Figure 1.
Radiotherapy plan delivered (A), contrast-enhanced CT 1 month after SBRT (B) and 5 months after SBRT (C). Blue line: planning target volume, yellow line: internal target volume.
The patient was immobilized in a vacuum cushion device. Abdominal compression was utilized to mitigate respiratory motion. Contrast-enhanced axial CT images were obtained with a slice thickness of 2.5 mm. A 4-dimensional CT (4DCT) image series was obtained to account for target motion throughout the respiratory cycle and processed to generate a maximum intensity projection. Structure delineation, treatment planning and optimization were performed using RayStation® Version 6 (RaySearch Laboratories AB, Stockholm, Sweden).
The gross tumor volume (GTV) within the spleen was delineated. No clinical target volume (to account for microscopic disease) was utilized. An internal target volume (ITV) was delineated using 4DCT. The planning target volume (PTV) comprised a 5 mm isotropic expansion of the ITV (volume: 58.74 cm3). A dose of 50 Gy in 10 fractions was prescribed to the PTV due to the target’s proximity to hollow viscera such as large bowel and stomach. Volumetric modulated arc therapy was utilized (Figure 1A). Optimization was performed to achieve 100% of the ITV receiving at least prescription dose and at least 95% of the PTV to be covered by the prescription isodose line. The maximum dose was 67.4 Gy (135%). The Lomax conformity indices for the prescription dose and 50% isodose were 0.96 and 0.27, respectively. Previously-published 10-fraction dose-volume constraints were met [4]. Treatment was delivered with daily cone-beam CT (CBCT) image guidance. The patient was aligned to external marks and the couch was shifted to align the CBCT to the reference. The average 3D vector of target motion was 0.48 ± 0.24 cm.
She experienced no apparent acute toxicity during treatment. Mild fatigue and transient anemia (Grade 1, CTCAE version 5) were noted during the weeks immediately following treatment.
Post-treatment CT revealed interval decrease in the treated lesion: 1.6 cm in maximum diameter at 1 month post-treatment (Figure 1B) and 0.9 cm at 5 months (Figure 1C). Total spleen volume decreased from 465 cm3 to 375 cm3 at 5 months. At her last follow-up 12 months post-treatment, she was clinically without evidence of disease, CA-125 was 20.59, and she had developed no late toxicity.
Discussion
Splenic metastasis from solid malignancies is a relatively rare phenomenon. A recent series reviewing over 6,000 patients with metastatic disease from any primary site identified splenic metastases in approximately 1% [8]. Another review documented 34 cases of splenic metastases of ovarian carcinoma, of which 17 were isolated or solitary [9]. These occurred an average of 5.5 years (range 1-20) after initial surgery. With such a long natural history, this disease process represents a unique clinical scenario when considering radical local therapies.
Since data for spleen SBRT are limited, it is necessary to utilize previously-reported normal tissue dose constraints to generate a safe radiotherapy plan. Institutional standard normal tissue tolerances for 10-fraction SBRT that have been reported in a prospective clinical trial were utilized to minimize the risk of toxicity to adjacent organs at risk [4] Additionally, UK consensus guidelines exist for various fractionations [10]. NRG-BR002 (NCT02364557) has also delineated dose limits developed from a preceding phase 1 trial. The patient in the current study was free from symptomatic toxicity 1 year after treatment, providing further evidence of the safety of the selected fractionation and dose constraints utilized.
In summary, oligometastatic disease to the spleen is a rare phenomenon. Recent evidence has emerged supporting local ablative therapy for patients with limited metastatic disease from various primary malignancies. We report the case of a patient with oligometastatic ovarian serous carcinoma who was treated with SBRT to an isolated splenic metastasis with minimal observed toxicity and excellent local control. SBRT represents an attractive alternative to splenectomy in select patients. Further investigation is warranted to ensure efficacy and safety.
Acknowledgements
Authors’ disclosure of potential conflicts of interest
The authors have nothing to disclose. The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Army, Department of Defense, or the U.S. Government.
Author Contributions
Conception and design: Ryan Hughes, Michael Soike, Michael Farris
Data collection: Ryan Hughes, Michael Soike, Surendra Prajapati
Data analysis and interpretation: Ryan Hughes, Michael Soike, Surendra Prajapati, Andrew Lin, James Ververs, Adrianna Masters, Corbin Helis, A. William Blackstock, Michael Farris
Manuscript writing: Ryan Hughes, Michael Soike, Surendra Prajapati, Andrew Lin, James Ververs, Adrianna Masters, Corbin Helis, A. William Blackstock, Michael Farris
Final approval of manuscript: Ryan Hughes, Michael Soike, Surendra Prajapati, Andrew Lin, James Ververs, Adrianna Masters, Corbin Helis, A. William Blackstock, Michael Farris
Compliance with Ethical Standards:
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee (Wake Forest School of Medicine Institutional Review board #IRB00046427) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent was waived, as there was no identifiable data reported in this study.
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