ORIGINAL ARTICLE – ENDOCRINE TUMORS
Adjuvant Radiation is Associated with Improved Survival
for Select Patients with Non-metastatic Adrenocortical Carcinoma
Daniel W. Nelson, DO
, Shu-Ching Chang, PhD
, Brad C. Bandera, MD
, Trevan D. Fischer, MD
Robert Wollman, MD
, and Melanie Goldfarb, MD, MS, FACS, FACE
Division of Surgical Oncology, John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica,
Department of Biostatistics, Medical Data Research Center at Providence Health and Services Center, Portland, OR;
Department of Radiation Oncology, Providence Saint John’s Health Center, Santa Monica, CA;
Center for Endocrine
Tumors and Disorders, John Wayne Cancer Institute at Providence Saint John’s Health Center, Santa Monica, CA
Background. Adrenocortical carcinoma (ACC) is a rare
and aggressive malignancy for which surgery is the
mainstay of treatment and for which adjuvant radiation is
infrequently employed; however, small, single-institution
series suggest adjuvant radiation may improve outcomes.
Methods. All patients with non-metastatic ACC treated
with either surgery alone or surgery followed by adjuvant
radiation were identiﬁed in the 2004–2013 National Cancer
Database. Factors associated with receipt of radiation and
the impact of adjuvant radiation on survival were deter-
mined by multivariable analysis.
Results. Of 1184 patients, 171 (14.4%) received adjuvant
radiation. Patient demographics were similar between the
two groups, but those receiving radiation were more likely
to have had positive margins following surgery (37.4 vs.
14.6%; p \ 0.001), evidence of vascular invasion (14.0 vs.
5.1%; p=0.05), and receive concurrent chemotherapy
(57.3 vs. 28.8%; p \ 0.001). After adjustment for tumor
and other treatment factors, only positive margins follow-
ing surgery was associated with an increased likelihood of
receiving adjuvant radiation (odds ratio 3.84, 95% conﬁ-
dence interval [CI] 1.95–7.56). Radiation therapy did not
confer a difference in median overall survival in the
general cohort. However, for patients with positive mar-
gins, adjuvant radiation was associated with a 40%
decreased yearly risk of death after adjustment for con-
current chemotherapy (hazard ratio 0.60, 95% CI
0.40–0.92; p=0.02). This survival advantage was not
evident for other traditional high-risk features.
Conclusion. Adjuvant radiation appears to decrease the
risk of death in ACC patients with positive margins fol-
lowing surgical resection, but only a small percentage are
currently receiving radiation. Multidisciplinary treatment
with surgery and radiation should be considered for these
Adrenocortical carcinoma (ACC) is well-recognized as
a rare but highly aggressive malignancy. Although the
annual incidence ranges between just 0.5 and 2.0 per mil-
patients commonly present at advanced stages,
leading to poor overall prognosis,
which has not signiﬁ-
cantly changed over the last 4 decades.
Based on the
European Network for the Study of Adrenal Tumors
(ENSAT) staging classiﬁcation, estimates of 5-year dis-
ease-speciﬁc survival are 82% for stage I, 61% for stage II,
50% for stage III, and 13% for stage IV.
The mainstay of treatment for ACC is complete radical
resection with negative margins; however, local recurrence
is common and, in historical series, has been reported to
occur in as many as 85% of patients.
Repeat resection of
recurrent disease has been shown to improve survival
has often been relied upon as ‘adjuvant therapy’ due to
limited options for efﬁcacious systemic alternatives.
Adjuvant radiation has been proposed as a means to
reduce high recurrence rates in ACC following surgery
with curative intent. Early series examining the utility of
Poster presented at the 125th Annual Meeting of the Western Surgical
Association, Scottsdale, AZ, USA, 5 November 2017.
Ó Society of Surgical Oncology 2018
First Received: 2 February 2018;
Published Online: 10 May 2018
M. Goldfarb, MD, MS, FACS, FACE
Ann Surg Oncol (2018) 25:2060–2066