3 Discussion
According to the National Comprehensive Cancer Network (NCCN), carotid
artery invasion is a sign of poor prognosis, such as oral cavity cancer,
P16—oropharyngeal cancer, laryngeal cancer,
hypopharyngeal cancer other than nasopharyngeal cancer. MR images were
used to predict carotid artery invasion [9]: circumferential
involvement of 270° or less of the wall meant no invasion, and more than
270° meant wall invasion. Based on our comparison of the survival rates
in three degrees of carotid artery invasion (<180°,
180°≤IG<270°, and ≥270°), although the difference was not
statistically significant, it showed that the survival rate tended to
decrease with an increase degree of invasion. However, patients with
LANC with carotid artery invasion have a better prognosis, compared with
other head and neck tumors. In this study, 130 LANC patients with
carotid artery invasion were treated with induction chemotherapy
followed by CCRT ± an EGFR inhibitor. Five-year survival rates were:
PFS=75.2%; DMFS=76.8%; LNRFS=90.0%; LRFS=93.9%; NRFS=95.8% and
OS=87.2%. Side effects were mild and well-tolerated; survival rates
were similar to those observed in other studies [10-11].
Shen C et al. [12] showed that anemia is closely related to tumor
hypoxia, which may lead to tumor resistance to radiotherapy and
treatment failure. In this study, we found that the 5-year OS of
patients with the lowest hemoglobin levels (≤110 g/L) was significantly
lower than that of patients with hemoglobin levels >110 g/L
during radiotherapy. Therefore, we believe that patients should actively
monitor and treat anemia.
Other studies have shown that patients whose primary tumor located in
the pharyngeal recess, and who experienced inflammation and an opening
incisor tooth distance <1 cm, had a greater probability of
fatal bleeding after radiotherapy [13]. Yamazaki et al. [14] and
Cheng et al. [15] believed that the pharyngeal recess is part of the
petrosal region of the internal carotid artery where the tumor easily
invades the internal carotid artery and surrounding bone. If the
pharyngeal recess infected, the surrounding tissues may become necrotic,
which may cause rupture of the internal carotid artery and fatal
bleeding. Similarly, the primary site of the three cases were all the
pharyngeal recess, with more than 270 º carotid artery invasion and
restricted mouth opening.
Fatal bleeding is common in previous studies, Zheng et al. [16]
found that 1.5% of nasopharyngeal carcinoma patients with IMRT
experienced fatal bleeding. Wu et al.[13] showed that 52.9% (45/85)
of such patients (stage I-IV) occurred fatal bleeding, with 20 patients
died. In our study, all patients were stage III-IV, 32 cases with
carotid artery invasion <180° and 37 cases with
180°≤IG<270°, no patients suffered fatal neck hemorrhage.
Sixty one patients with carotid artery invasion ≥270°, among whom three
patients died of neck hemorrhage, the overall incidence was only 2.3%
(3/130), which was attributable to nasopharyngeal necrosis (2 of whom
were diabetics and 1 received re-radiation after recurrence). Most
scholars believe that radiation, trauma and infection cause
nasopharyngeal necrosis [14]. Re-radiation increases the risk of
necrosis of the nasopharynx and neck hemorrhage [17]. The 2
diabetics had uncontrollable infection with local necrosis. The patient
who received re-radiation was exposed to a cumulative radiation dose of
137.5 Gy and developed osteoradionecrosis of the nasopharynx seven
months after radiotherapy. Another patient with the primary site of the
nasopharyngeal wall was treated with surgery after recurrence, and he
survived without fatal bleeding. Surgery may be a better option than
re-radiation for patients with carotid artery invasion ≥270° who
experience recurrence.
In our study, 127 patients without massive hemorrhage benefited from the
application of induction/concurrent chemotherapy and HT. Induction
chemotherapy can reduce tumor load, enlarge the space between the
carotid artery and the tumor body and produce a greater safety margin,
thereby reducing damage to important tissues and organs caused by
radiotherapy. Dionisi et al. [18] showed that CCRT could further
shrink the tumor body, accelerate blood supply to surrounding tissues,
and reduce the incidence of mucosal necrosis. HT has many dosimetric
advantages, such as delivering a more precise dosage to the target
tissue(s) and reducing radiation exposure to critical surrounding
organs, thereby improving local control with less radiation damage
[19]. In addition, multivariate analysis showed that use of an EGFR
inhibitor was an independent prognostic factor for PFS and DMFS.
Previous studies have shown that adding CTX/NTZ to CCRT may improve OS,
DFS and DMFS [20-24], which is consistent with our results. EGFR
inhibitors also have been shown to have significant anti-proliferation,
pro-apoptosis and anti-angiogenesis effects, which may further control
the recurrence of tumors and improve the sensitivity of tumors to
radiotherapy and chemotherapy [25].
In conclusion, 130 patients with LANC surrounding the carotid artery
were treated with a comprehensive treatment regimen, 95.7% of the
patients successfully completed the entire courses, producing desirable
outcomes and a low incidence of fatal hemorrhage. Improved outcomes may
be possible with the application of new proton and other radiotherapy
technologies and new PD-1 immuno-targeted drugs in patients with
nasopharyngeal carcinoma. The primary site located in the pharyngeal
recess with more than 270 º carotid artery invasion and restricted mouth
opening, especially diabetics, should actively control blood glucose
levels and prevent infection. Nasopharyngeal necrosis should be actively
treated by antibiotics and hyperbaric oxygen, removing by oxygen nasal
endoscope regularly.
Abbreviations: Arrowheads indicate the ICA; LANC, Locally
advanced nasopharyngeal carcinoma; MRI, magnetic resonance imaging; ICA,
internal carotid artery; T1WI, T1-weighted imaging
EGFR, epidermal growth factor receptor inhibitor; PFS, progression-free
survival; DMFS, distant metastasis-free survival; LNRFS, local nodal
recurrence-free survival; LRFS, local recurrence-free survival; NRFS,
nodal recurrence-free survival; OS, overall survival
T: docetaxel; P: cisplatin; F: 5-fluorouracil; G: Gemcitabine; D:
Doxorubicin
HR3, Nimotuzumab; C-225, Cetuximab; HT, helical tomography