Efficacy and safety of radiation therapy in advanced adrenocortical carcinoma

Abstract

Background International guidelines emphasise the role of radiotherapy (RT) for the management of advanced adrenocortical carcinoma (ACC). However, the evidence for this recommendation is very low. Methods We retrospectively analysed all patients who received RT for advanced ACC in five European centres since 2000. Primary endpoint: time to progression of the treated lesion (tTTP). Secondary endpoints: best objective response, progression-free survival (PFS), overall survival (OS), adverse events, and the establishment of predictive factors by Cox analyses. Results In total, 132 tumoural lesions of 80 patients were treated with conventional RT (cRT) of 50–60 Gy (n = 20) or 20–49 Gy (n = 69), stereotactic body RT of 35–50 Gy (SBRT) (n = 36), or brachytherapy of 12–25 Gy (BT) (n = 7). Best objective lesional response was complete (n = 6), partial (n = 52), stable disease (n = 60), progressive disease (n = 14). Median tTTP was 7.6 months (1.0–148.6). In comparison to cRT20-49Gy, tTTP was significantly longer for cRT50-60Gy (multivariate adjusted HR 0.10; 95% CI 0.03–0.33; p < 0.001) and SBRT (HR 0.31; 95% CI 0.12–0.80; p = 0.016), but not for BT (HR 0.66; 95% CI 0.22–1.99; p = 0.46). Toxicity was generally mild and moderate with three grade 3 events. No convincing predictive factors could be established. Conclusions This largest published study on RT in advanced ACC provides clear evidence that RT is effective in ACC.

Current Evidence on Local Therapies in Advanced Adrenocortical Carcinoma

“…In our study with 80 patients, we reported 43 grade 1 adverse events including fatigue, anaemia, skin, hepatic, renal, intestinal, and pulmonary toxicities. In addition, we observed 13 grade 2 adverse events with fatigue, musculoskeletal disorders, skin, pulmonary, and intestinal toxicities, and three grade 3 adverse events (with pulmonary and intestinal toxicities) (26). Both of these studies reported no grade 4 or 5 adverse events.…”

“…Thus, we conclude that RT seems to be mostly well-tolerated and effective in the management of metastatic ACC, controlling local symptoms, and preventing complications from large metastases. More recent data clearly suggest that higher radiation dosages (e. g., > 50 Gy) or stereotactic body radiotherapy might -not surprisingly -be more effective in achieving objective tumour response [26].…”

“…We reported 38 (29 %) patients with a mitotane therapy and a mitotane level > 14 mg/l during RT. However, mitotane treatment had no significant influence on RT treatment response [26]. Roux et al also included patients with mitotane treatment during RT.…”

High-Dose Rate Brachytherapy Combined with PD-1 Blockade as a Treatment for Metastatic Adrenocortical Carcinoma – A Single Center Case Series

“…Radiotherapy plays an increasing role in the treatment of ACC. It can be beneficial both adjuvantly, in patients at high risk of recurrence [19], but also in the management of metastases [20][21][22]. Radiotherapy is therefore recommended by current guidelines for the control of imminent complications or oligometastatic disease [23].…”

The Adrenal Gland: A Fascinating Object of Research and Clinical Care Showcased at the 15th German Adrenal Conference in Dresden

“…The manuscripts by Kimpel et al [7] and Schwarzlmueller et al [8] complement each other in underscoring the utility of localized treatment in metastatic adrenocortical carcinoma (ACC). While firm conclusions on some modalities are hampered by the heterogeneity of local practice and expertise, it appears that radiotherapy may be particularly useful for local control of ACC.…”