4. Discussion
With the development of treatments, only 10-20% NPC patients would
suffer local recurrence after initial treatment29-31.
Surgery was one of options for recurrent NPC. In most retrospective
studies, surgery has been reported to achieve a similar or better result
than re-irradiation with a 5-year LC of 43-74% and a 5-year OS of
47-62%9-13. Moreover, the advantage of surgery was
fewer complications and better quality of life. However, it might be due
to selected patients. The lesions considered resectable included rT1
disease, rT2-3 with limited parapharyngeal space involvement or disease
confined to the base of sphenoid sinus. Others, such as involvement of
the internal carotid artery, limited invasion to the clivus, posterior
maxillary sinus, pterygoid process and petrous apex, might be
resectable, which required the careful judgment by
surgeon32. Therefore, there were still many patients
not suitable or willing to receive surgical treatment, especially those
with late-stage recurrence.
Reirradiation was the most common salvage treatment for recurrent NPC,
especially for those unable to receive surgery18.
However, previous studies have shown that recurrence usually occurred in
high-dose areas with the characteristic of
radio-resistance3334. Moreover, when finishing the
first course of radiation, changes in the microenvironment such as
fibrosis and vascular necrosis might exacerbate
radio-resistance35. Reirradiation became a stuff work
because of the balance of high dose needed for radio-resistance tumors
and dose limited by accumulation of surrounding organs at risks.
Previous studies have shown that the recurrent NPC patients with
re-irradiation as a salvage treatment, LC and OS at 3 years can reach
70-89% and 46-58%, respectively19-22. However, the
side effects of reirradiation remain challenging issues. Virtually most
patients with irradiation suffered long-term complications. About
30-70% of patients were likely to develop severe (grade 3-5)
complications 202123-25. Moreover, some patients might
die of fatal complications, such as necrosis of the temporal lobe
necrosis, carotid blowout, teeth occlusion and mucosal
ulcer26[23,40,41]. Han and
colleagues21reported that the prevalence of advanced
toxicity (grade 3-5) of intensity modulated radiotherapy (IMRT)for
treatment of recurrent NPC was 70.3%, and that 69 % of patients died
of EBRT-related toxicity. Kong and co-workers19reported that 29.3% patients died of radiotherapy-related
complications. Of these patients, 23.9% patients died of massive
hemorrhage, indicating that massive hemorrhage was the most common cause
of death. 75%of patients underwent locally advanced disease. Koutcher
and colleagues36 reported an incidence of 73% that
grade III or above complications occurred. Teo and
co-workers37 reported that the incidence of hearing
loss or difficulty in opening mouth was approximately 50-70% after
reirradiation.
125I RSI-BT, one of the most common brachytherapy, was
often chosen as a salvage treatment for recurrent cancers, such as
hypopharyngeal carcinoma38, salivary gland
carcinoma39 or other head and neck squamous cell
carcinoma40. Because of its sharp dose curve,125I RSI-BT could protect OARs and achieve a higher
local dose distribution so as to achieve favorable LC. Many published
studies40-46 have reported RSI-BT as a safe and
effective treatment for recurrent NPC, with a local control probability
at 1- and 3-years of 52-75.2% and 5.3-73%, respectively, and an
overall survival probability at 1- and 3-years of 53-84.6% and
6.7-39%, respectively, as well as a accepted toxicities(Table 4).
In this retrospective analysis, LC of RSI-BT as a salvage treatment for
recurrent NPC at 1-, 3- and 5-year was 71.3%, 41.9% and 27.9%,
respectively and OS at 1-, 3- and 5-year was 57.7%, 23.8% and 11.9%,
respectively, which just the same as published studies.
We found that the total times of previous EBRT was a prognostic factor
affecting LC (P=0.001) and OS (P=0.012). For patients those received
only once EBRT, LC at 1, 3 and 5 years was 93.8%, 58.6% and 58.6%,
respectively and OS at 1-, 3- and 5-years was 72.3%, 36.3% and 18.1%,
respectively. However, for those received EBRT twice or three times, LC
at 1, 3 and 5 years was 42.4%, 25.5% and 0%, respectively and OS at
1- and 3-years was 31.2% and 0%, respectively. The results were
probably due to fibrosis, atrophy and necrosis of local tissue, vascular
redistribution, and decreased radio-sensitivity after multiple EBRT.
Salvage treatment for local recurrent NPC after previous EBRT was a
stuff task especially when the patient experienced twice or more courses
of EBRT and RSI-BT might be alternative and promising.
We also found that sex was a key factor affecting LC (P=0.037), which
was not reported in previous work. It needs to be further investigated
to exclude cause of the patient pool’s unbalanced sex ratio males to
females and small study cohort.
The use of 3D-PT might improve LC (P=0.078) though the statistically
difference was less significant. 3D-PT was creatively designed and
introduced into CT-guided RSI technique47. With 3D-PT
assistance, RSI-BT may be more accurate and have better doses
distribution which close to expected preoperative
plan48. It provided a way of RSI-BT to standardization
and normalization. An ideal dose distribution may lead to a better LC,
but we can only identify the tendency due to our limited case number and
still need more data to confirm it.
KPS was a prognostic factor to LC (P=0.033) and might be a prognostic
factor to OS (P=0.075) though the statistically difference was less
significant, which might have been due to the small study cohort or
confounding factors. However, this prognostic factor needed more data to
verify.
Furthermore, safety was another key point needed to be paid attention
to. Comparing to EBRT, RSI-BT has the advantage of providing a small
radius of radiation, high local radiation dose, sharp fall-off of the
radiation dose and few radiation effects on adjacent tissues. These
features achieve the goal of Precise EBRT and 125I
RSI-BT been recommended for treatment of several types of recurrent or
relapsed cancer by the National Comprehensive Cancer Network. In our
study, only 2 cases (6.5%) suffered severe radiotoxicity: 1 case with
of grade 3 skin/mucosal toxicity and another of mandibular
osteonecrosis. Besides, eleven patients (41.9%) suffered from late
grade 1-2 adverse effects, including ten cases (32.2%) of skin/mucosal
toxicities and one case (3.2%) of pain. The prevalence of severe toxic
and side effects observed in our study was obviously lower than that of
patients receiving reirradiation for recurrent NPC in other studies, and
further demonstrated the safety of 125I RSI-BT for
treatment of recurrent NPC.