Discussion
Brachytherapy is an essential part of cervical cancer treatment. It is
able to provide the maximal dose to the target area while minimizing the
dose to OARs. Previous studies demonstrated that ICBT is a safe,
effective modality for cervical cancer28. However, tumors
with large residual disease after EBRT present a therapeutic challenge.
Attempts have been made to improve tumor dose coverage by ICBT.
Optimization of pear shaped isodose configuration is an easy and simple
method but it is limited because of the limited number of source
position. Other dosimetric studies have investigated the possibility
replacing ICBT with IMRT or stereotactic body radiotherapy (SBRT)29-31. One must also
consider the uncertainty of interfraction and intrafraction motion of
the target due to bladder and rectal filling30-32. Hybrid IC/ISBT
is a relatively new technique using intra-cervical interstitial
brachytherapy to improve the target volume coverage8. Multi-institutional
clinical studies, retroEMBRACE and EMBRACE-I, have investigated a large
number of patients and confirmed favorable clinical outcome and
acceptable toxicity 20,
33.
EMBRACE-II
was launched as a prospective study based on the outcome results of
retroEMBRACE and EMBRACE-I with IC/ISBT34.
In 2008, Duan et al 23and Assenholt et al 35reported that a combination of ICBT with IMRT boost maintained the dose
distribution and characteristics of ICBT while adequate tumor dose
coverage was achieved by supplementary IMRT (IC/IMRT). Comparative
dosimetric studies between conventional ICBT, optimized 3-D ICBT and
IC/IMRT confirmed that IC/IMRT has better target volume coverage for
large tumors while maintaining low dose to OARs35-37. One unique
feature of IC/IMRT is this treatment is carried out with the applicator
in situ to provide spatial registration and immobilization of the
gynecologic organs. After treatment of the ICBT, the supplementary IMRT
plan is executed immediately at the same position to ensure the accuracy
of target irradiation during the entire treatment process.
Our study included only patients with unfavorable large residual tumor
at the time of ICBT. Therefore, Mean HR-CTV volume was a much larger
volume (65.8 ± 23.6cc) than other studies. The mean HR-CTV volume was 34
± 17cc in Kirisits et al study38, 38 ± 20cc in
Tanderup et al
study39,
and 55 ± 38cc in Jurgenliemk-Schulz et al study40.Ken
Yoshida et al 41demonstrated that classical conventional ICBT is suitable for the
treatment of most HR-CTV size of 36cc or smaller tumors. For bulky
tumors patients who poorly responding to EBRT may increase the need for
more sophisticated brachytherapy, such as comprehensive interstitial
techniques, due to unfavourable geometry at the time of brachytherapy
implant. Therefore, it would seem reasonable that IC/IMRT is an
alternative to the IC/ISBT or ISBT modality to deliver the boost of dose
to the bulky tumors.
The DVH parameters of cervical cancer radiotherapy are related to the
local control rate and side effects. Dimopoulos et al42 retrospectively
analyzed 141 cervical cancer patients with 51 months median follow-up
and demonstrated that the HR-CTV D90 > 87Gy resulted in a
LC
rate of 96% compared to 80% for HR-CTV D90 < 87Gy.
Pötter
et al 8 reported that
the average D90 dose of HR-CTV in 156 patients treated with HDR-ICBT was
93 Gy, resulting in a 3-year LC rate of 95%. Lindegaard et al43 reported that
patients treated by HDR-ICBT with the average HR-CTV D90 doses of 91 Gy
had an actuarial 3-year pelvic control rate of 85%. The retroEMBRACE
study44 showed that
with the systemic usage of IC/IS the D90 of HR-CTV increased 9Gy from 83
± 14Gy to 92 ± 13Gy and 3-year local control rate in patients having a
HR-CTV ≥ 30cm3 was 10% higher in IC/IS group.
In our study, the average D90 doses of HR-CTV and IR-CTV in 76 cases
were 88.7 Gy and 78.1 Gy, respectively. The V100 of HR-CTV was more than
90%. Estimated Local recurrence free survival rate at 5 years was
87.6% for all investigated patients, respectively. Estimated metastasis
recurrence free survival rate at 5 years was 82.4%. The estimated
overall actuarial cancer specific survival at 5 years was 76.3%, the
disease free survival at 5 years was 70.9%, respectively.
The side effects of image-guided brachytherapy have been relatively low.
The EMBRACE studies showed that a D2cc ≥ 75 Gy was associated with
12.5% risk of fistula and 2.7% with low dose at 3 years. A D2cc
< 65 Gy was associated with a two times lower risk of
proctitis than ≥ 65 Gy in 960 patients45. Grade 3 to 4
urinary morbidity was 5.3% in 1176 patients46. French STIC
prospective study 19showed that 3-D imaging based plan reduced Grade 3 to 4 toxicities than
2-D plan, 2.6% and 22.7% respectively in 117 patients. Our study
showed that the crude grade 3 late toxicities were 3.9%
gastrointestinal and 5.2% urinary system. Neither crude grade 4 acute
nor late toxicities were found in gastrointestinal and urinary systems.
Actuarial rate for G3 + G4 morbidity was 2.6%/3.9% for the GI,
3.9%/5.2% for the GU at 3/5 years, respectively. Our mean D2cc for
OARs was comparable with other studies (bladder 71.8, rectum 64.6,
sigmoid colon 63.9 and intestine 56.7 Gy).
Several limitations in our study should be acknowledged. This is a
retrospective and single institutional study. Also, due to time
limitation, an IMRT-QA check was not done before the IMRT treatment was
delivered.
Based on our experience, we would like to emphasize the following
points. The IC/IMRT technique can be logistically challenging if the
procedure is not orchestrated in proper order. First, the time between
ICBT and IMRT should be as short as possible to maintain applicator
stability and patient comfort. Second, complementary IMRT was designed
to compensate the dose of ICBT due to the lack of dose coverage from
ICBT alone, thus the ICBT always contributed the majority of the dosage
in this technique, which is important to reduce the dose for OARs.
Finally, patient selected criteria needs to be defined for using IC/IMRT
in the future. IC/IMRT is potentially less invasive, and a more
applicable treatment than IC/ISBT and ISBT. IC/IMRT is another
alternative technique when IC/ISBT or ISBT is not feasible.