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Journal of International Medical
http://imr.sagepub.com/content/40/6/2346
The online version of this article can be found at:
DOI: 10.1177/030006051204000633
2012 40: 2346 Journal of International Medical Research
Z Liu, Y Gao, YL Soong, X Chen, F Gao, W Luo, W Sheng, J Ren, L Zhang and J Wang
Cervical Cancer: A Retrospective Study
Intraoperative Electron Beam Radiotherapy for Primary Treatment of Stage IIB
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2351
Z Liu, Y Gao, YL Soong et al.
IOERT in cervical cancer
Discussion
This retrospective study of IOERT as primary
treatment for cervical cancer indicated
significantly improved overall survival,
disease-free survival and local control
compared with RT. The 5-year overall
survival and disease-free survival rates for
cervical cancer have been reported as 72.2%
and 65.8%, respectively,
2
which are
comparable with to the findings in the RT
group, in the current study. Overall and
disease-free survival rates were significantly
higher in the IOERT group than in the RT
group (Table 2), but further studies in a
clinical trial setting are required in order to
confirm this finding. Locoregional control
rates at 5 and 10 years were significantly
higher following IOERT compared with
radiotherapy. There was no between-group
difference in the rate of distal metastasis in
the present study, which was expected due to
the local nature of IOERT.
Intraoperative electron bean radiotherapy
delivers a single high dose of radiation (18 20
Gy; D
EQD2
36 50 Gy). Studies have revealed
that stereotactic body radiotherapy provides
greater than expected efficacy than can be
predicted from clonogenic cell inactivation
alone.
22
A single high dose of radiation allows
delivery of a large equivalent dose of radiation
to the tumour, such that a single dose of IOERT
is 1.5 2.5 times more effective than the same
total dose of fractionated EBRT.
23 25
In
addition, IOERT is applied during surgery,
rather than at a much later time point (as is
required with conventional EBRT), in order to
avoid interfering with wound healing.
26
An
additional advantage of IOERT is that the risk
area can be assessed intraoperatively,
allowing tailoring of the radiation field. The
fact that the patient is unconscious and
immobile during surgery further increases the
accuracy of IOERT.
27,28
Both treatment methods in the present
study resulted in approximately the same
dose of radiation being delivered to ICRU
point A. The total dose delivered to point A by
RT was D
EQD2
80 Gy, comprising D
EQD2
30 Gy
EBRT and D
EQD2
50 Gy brachytherapy. IOERT
delivered a total dose of D
EQD2
76 80 Gy
(EBRT D
EQD2
20 Gy + IOERT D
EQD2
36 50 Gy).
It is possible that the improved local control in
IOERT was a result of surgical removal of the
tumour and the ability to deliver radiation
accurately to areas at risk of microscopic
disease. The rates of bowel and bladder injury
TABLE 4:
Complications in patients with stage IIB
17
cervical squamous cell carcinoma following
primary treatment with intraoperative electron beam radiotherapy (IOERT) or radical
radiotherapy (RT)
IOERT RT Statistical
Complication n = 78 n = 89 significance
a
Rectal injury 4 (5.1) 27 (30.3) P < 0.05
Bladder injury 1 (1.3) 9 (10.1) P < 0.05
Pelvic pain and peripheral neuropathy 9 (11.5) 10 (11.2) NS
Hydronephrosis 10 (12.8) 5 (5.6) NS
Lower leg oedema 1 (1.3) 2 (2.2) NS
Total 25 (32.1) 53 (59.6) P < 0.05
Data presented as n (%) of patients.
NS, not statistically significant (P 0.05).
a
2
-test.
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2352
Z Liu, Y Gao, YL Soong et al.
IOERT in cervical cancer
were lower in the IOERT group than in the RT
group, probably due to the careful shielding
employed during irradiation. In addition,
some patients in the IOERT group received
brachytherapy after a comparatively low dose
of EBRT (8 16 Gy, compared with 30 Gy in
the RT group), with the result that most of the
high-dose region was likely to fall within the
gross tumour. This is compared with the RT
group, where the tumour would have shrunk
significantly by the time that brachytherapy
was delivered.
The use of combined surgery and RT is not
recommended for the treatment of early
stage cervical cancer
29
because of the
increased risk of severe toxicities.
30
Data
regarding the rate of complications after
IOERT are inconclusive, with some showing
no difference in complications
31
and others
finding an increase in adverse effects.
32
The
reduced rate of adverse effects with IOERT
compared with radiotherapy in the present
study may be due to the use of simple
hysterectomy with limited nodal dissection,
rather than radical hysterectomy and
complete pelvic lymph node dissection, thus
reducing the duration of surgery and
limiting the extent of injury to healthy
tissue. In the IOERT group in the present
study, the radiation dose to the bowel and
bladder was limited by moving the organs
away from the applicator during irradiation,
and the known low level of radiation
leakage (5%) from the applicator itself.
21
In the present study, the incidence of pelvic
pain and peripheral neuropathy was similar
in both treatment groups. The rates of
chronic pelvic pain and peripheral
neuropathy following IOERT have been
shown to range between 10 and 30%.
16,33,34
Rates of other complications, including
hydronephrosis and oedema of the lower leg,
were also similar between the groups. All
cases of toxicity were managed using
conservative treatment.
This study has several limitations. First, its
retrospective and nonrandomized nature
may have resulted in selection bias: fitter
patients could have chosen surgery and
patients with more comorbidities could have
chosen radiation alone, leading to differences
in overall survival. Secondly, chemo radio -
therapy is recommended for treatment of
locally advanced cervical cancer, but none of
the patients in the current study received
concurrent chemotherapy. It is therefore
unclear what impact, if any, this would have
had on the outcome. Thirdly, the grading of
toxicities was not performed consistently and
it was therefore not possible to report any
data regarding the severity of adverse events.
Finally, the optimal IOERT dose is not known.
Doses ranging from 10 30 Gy have been
reported.
31,35,36
Whether a lower dose would
reduce toxicities, or a higher dose would
further improve local control, is not known.
In conclusion, the present study findings
indicate that IOERT is an effective treatment for
stage IIB cervical squamous cell carcinoma,
resulting in enhanced local control and
improvements in disease-free and overall
survival compared with RT, without an increase
in complications. IOERT does not prevent
distant metastasis, however, and more effective
systemic therapies should be evaluated.
Conflicts of interest
The authors have no conflicts of interest to
declare in relation to this article.
Acknowledgements
This work was supported by grants from the
National Natural Science Foundation of
China (No. 81071838), Shaanxi Province
Department of Health Key Program (No.
2010A02) and the Foundation of the First
Affiliated Hospital of Medical College of
Xian Jiao Tong University (No. 2010YK3).
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Received for publication 20 May 2012 Accepted subject to revision 27 May 2012
Revised accepted 22 August 2012
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Authors address for correspondence
Dr Zi Liu
Department of Radiation Oncology, First Affiliated Hospital, Medical College of Xian
Jiaotong University, 277 Yanta West Road, Xian 710061, China.
E-mail: liuzmail@163.com
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IOERT in cervical cancer
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