Clinical efficacy of Stereotactic Body Radiation Therapy (SBRT) for adrenal gland metastases: A multi-center retrospective study from China

Abstract

To evaluate the efficacy and safety of CyberKnife Stereotactic Body Radiation Therapy (SBRT) in the treatment of adrenal gland metastases (AGM), we designed a large-scale multicenter retrospective study to report the safety and efficacy of SBRT for inoperable AGM. In this study, 75 (61 males, 14 females) patients with 84 AGM and Karnofsky performance score ≥70 were treated by SBRT from October 2006 to January 2017. Of these, the purpose of treatment were controlling all known metastatic sites for 21 patients while 54 for palliation of bulky adrenal metastases. The efficacy and safety of SBRT were evaluated during follow-up. Potential factors predictive of local control (LC) and overall survival (OS) were identified by univariate and multivariate analysis. Median follow-up time was 12.7 months (range 1.8-96.4). The complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD) rates were 23.8%, 23.8%, 31.0% and 21.4%, respectively. The 0.5, 1, and 2-year LC rates were 93.6%, 83.8%, and 62.1%, respectively; OS rates on the same follow-up intervals were 93.7%, 62.5%, and 49.6%, respectively, and the corresponding PFS rates were 48.5%, 33.9%, and 16.0%, respectively. The treatment was well tolerated with 2 patients reporting grade-3 diarrhea and fatigue, respectively. Multivariate analysis showed that simultaneous treatment of SBRT for other metastatic lesions, the number of AGM, initiation of systemic therapy, and the maximum diameter of AGM were predictive of LC rates. Moreover, patients with AGM < 5 cm had a superior OS compared with those with AGM ≥ 5 cm (28.0 months vs. 17.6 months, P = 0.032). SBRT is an effective therapeutic option for treatment of AGM with high LC rates with minimal toxicity. The adrenal gland is one of the commonest metastatic sites in primary tumors of lungs, liver, renal, colorectal, and lymphoma 1. Patients with adrenal gland metastases (AGM) have back or abdominal pain occasionally along with the growth of tumor 2. Rarely, patients with bilateral adrenal metastases may occur adrenal insufficiency which compromises quality of life (QOL) and results in worse outcomes 2. Although salvage chemotherapy and surgery are commonly used to treat AGM, limitations are inevitable. It is mandatory that pathological examinations of the primary tumor should be performed to guide decision making of chemotherapy regimens. Nevertheless, second-line chemotherapy may be less effective or may contribute to severe toxicities when the disease progresses after first-line chemotherapy has failed. Moreover, surgical resection may bring about adrenal insufficiency or other morbidities albeit it is regarded with curative intent 3. Hence, radiotherapy may be an alternative due to its potential efficacy and less risk of adverse effects compared to chemotherapy and surgery.

Stereotactic or conformal radiotherapy for adrenal metastases: Patient characteristics and outcomes in a multicenter analysis

“…This was done to facilitate comparability with other studies which mostly used unadjusted values. 30,34,42 The unadjusted LC differed between the arms and was in line with the two other larger datasets: after prescribed doses of 100, 80 and 60 Gy (BED10), Chen et al 32 found in their meta-analysis 3DCRT/IMRT were limited and statistical differences in FFLP might have been obscured by differences in histology, lesion size and systemic treatments. Furthermore, the minimum BED10 in the SBRT group was 50 Gy, a dose which is well below the BED10 of 100 Gy which is typically considered ablative, for example, in lung cancer which was the largest subgroup.…”

“…16,[22][23][24][25][26][27][28][29][30][31][32][33] Larger analyses include a retrospective database analysis conducted in Asian patients (n = 75) reporting 1-year LC rate of 83%. 34 Furthermore, multiple prospective and retrospective monocentric studies were included in a recent meta-analysis conducted by Chen et al, which reported a pooled 1-year LC rate of 82% with a strong association of prescribed doses and LC rates. 32 We conducted this multicenter database analysis of patients with adrenal metastases treated with SBRT or fractionated highly conformal RT (3DCRT/IMRT) within the framework of the SBRT database initiative of the Working Group Radiosurgery and Stereotactic Radiotherapy of the German Society for Radiation Oncology (DEGRO).…”

“…1-year LC rates of 92.9%, 84.8% and 70.5%; Zhao et al34 calculated an unadjusted 1-year LC estimate of 83.8% after an average BED10 of 79.6 Gy. In our cohort, the unadjusted 1-year FFLP-estimates were 80.8%, 60.6% and 57.7%, after average prescribed BED10 doses of…”

The role of immunotherapy in combination with oligometastasis-directed therapy: a narrative review

“…It is important to note that the doses of radiation used in these trials (with the exception of the patients in the MDACC trial randomized to combinedmodality therapy in whom 50 Gy in 4 fractions was deemed feasible) resulted in BEDs that are well below that of ablative approaches in which BEDs of 100 Gy and greater are delivered. Given that ablative BEDs have been demonstrated to be imperative for optimal local control of irradiated metastases (126)(127)(128)(129) and that degree of local response to SBRT is an important predictor of survival (112) future randomized studies investigating the role of SBRT in combination with ICB should utilize ablative doses of radiation therapy in an attempt to maximize the potential for therapeutic response with this liaison. Although the currently reported randomized studies do support the safety of SBRT in combination with ICB, it is important that future studies utilizing higher doses of SBRT evaluate this further as these, along with ongoing phase III studies investigating the combination of ablative doses of radiation with ICB in the definitive setting, will help to determine the safety of this approach.…”

“…In addition to attempts to increase the therapeutic ratio of SBRT and ICB, by altering the tumor microenvironment, improvements in metastasis-directed SBRT have the potential to significantly improve the efficacy of this treatment approach. As previously discussed, given that ablative BEDs are crucial for optimizing the local control of irradiated metastases (126)(127)(128)(129) and that local response to SBRT has been correlated with survival (112), randomized studies investigating the role of ablative doses of SBRT in combination with ICB are needed. Historically, technical and practical considerations have largely limited the feasibility of multi-site SBRT using ablative doses for patients with metastatic disease, though several recent innovations have significantly decreased these limitations.…”