Taiwan: Institutional Review Board

The optimal management of head and neck squamous cell carcinoma typically involves primary surgical resection, and the indications for adjuvant radiotherapy are based on pathologic markers of intermittent - and high-risk disease, which include positive margins, extracapsular nodal extension, lymphovascular invasion, and perineural invasion (1-3). Trismus is one of long term sequelae of radiotherapy for head and neck cancer patient. The prevalence of trismus after head and neck oncology treatment could be as high as 42% (4). It is significantly reducing nutrition due to impaired mastication (5). The loss of function appears to be related to damage and fibrosis to the muscles of mastication. Radiation therapy involving the temporomandibular joint, the pterygoid muscles, the temporalis or the masseter muscle is most likely to result in trismus (5, 6). Moreover, there may be scar tissue from radiation or surgery, nerve damage, or a combination of these factors (6, 7). In addition, the doses of RT levels in excess of 60 Gy (8) or the configuration of the radiation field increasing (9) are more likely to cause trismus. These data were documenting the clinical results of conventional radiotherapy (RT).

Recently, extensive data suggest that intensity-modulated radiation therapy (IMRT) is safe and efficacious in the adjuvant setting for oral cavity cancer (OCC) (10-12). Hsiung et al. (13) and Chen et al. (14) confirmed that radiation induced trismus progressed over time and improved by IMRT. Hsiung et al. (13) found the averages of normalized maximal interincisal distance (MID) were 94% and 98.1% at 5 ms and 12 ms post-IMRT, respectively. In addition, only 0.2 mm the deterioration of radiation-induced trismus in the period from 12-18 months post-IMRT was noted. Moreover, Chen et al. (14) also confirmed that radiation induced trismus progressed over time and improved by IMRT. However, Kent et al. (15) examined the incidence of trismus in IMRT group compared to conventional radiotherapy group. There was no significant difference in the maximum vertical dimension between the IMRT and the conventional RT groups, (38.8 ± 9.0 vs 33.7 ± 10.1 mm, respectively, p = 0.11).

Helical tomotherapy (HT) is conceptually regarded an image-guided IMRT. HT was designed and developed with advantages in sharper dose gradients and better normal tissue sparing. Our and the other clinical experience of using HT for locally advanced head and neck cancer had achieved encouraging results along with less toxicity, such lower percentage of dermatitis and xerostomia when compared with previous reports (16-18). HT provides better normal tissue sparing and sharper dose gradients than IMRT (19, 20).Chen et al. (19) compared HT and IMRT for nasopharyngeal carcinoma and noted that HT significantly reduced dose to the contralateral parotid gland and improved dose homogeneity to the PTVs. Additionally, HT reduced mean doses to brainstem (p = 0.02), larynx (p = 0.03), and oral cavity (p = 0.03). Similarly, for head-and-neck cancer, HT plans also provided favorably results compared with the step-and-shoot IMRT plans. They are expected to be able to reduce the parotid normal tissue (average 6.5 Gy) complication probability further, keeping similar target dose homogeneity (21). Furthermore, HT provided better mandible sparing than IMRT with mean dose decreased from 34.9 Gy (IMRT) to 30.7 Gy (HT) (20). However, can HT provide better normal tissue sparing to reduce the incidence of trismus? It's still an interesting issue to discuss.

In our 4-year initial clinical experience of 39 postoperative OCC patients treated with HT, we noted the incidences of grade 1 and grade 2, 3 trismus [according to the Common Terminology Criteria for Adverse Events v3.0 (CTCAE v3.0) ] appear inversely trend in time sequence with post-HT treatment (Fig. 1). These observations hint the possible of decreasing late complications of HT by better normal tissue sparing and sharper dose gradients (16-18) and responses to radiation induced trismus improved by IMRT (13, 14).

According to previous study (6), Magnetic resonance imaging (MRI) could provide advantage findings in masticator structures in patients with trismus developing after radiotherapy for nasopharyngeal carcinoma (NPC). The abnormalities comprising radiotherapy-induced masticator muscle fibrosis or inflammation, denervation atrophy of the masticator muscles secondary to mandibular nerve damage, osteoradionecrosis change of mandibular rami, perimasticator fibrosis extending into the masticator space and post RT damage of the parotid gland. The presence of several MRI abnormalities in the masticator structures of patients with trismus after radiotherapy suggests that trismus is multifactorial. However, there was no good correlation data between the severities of trismus with these image findings and thus these changes may possible due to non-specific inflammatory and fibrosis reactions after radiation. Also, there was no correlation data between radiation dosages with these abnormality, so all these findings may also result from other causes such as surgery or chemotherapy. Therefore, we try to evaluate MRI examinations performed in patients before and after trismus establishing following radiotherapy for OCC patients, in order to identify the range and frequency of underlying diseases that may cause this complication. We retrospect the OCC patients using MRI signal abnormality scores (SA score), separating the patient according to their clinical trismus grading into three groups, the mean SA score of grade 0 patient is 8.5, grade 1 is 6.76 and grade 2 is 4.87. Compared with group 2 patients, there are statistically significant differences between group 1 (p= .04) as well as group 0 (p= .02), respectively. It means the SA score could correspond to the trismus grade (Fig. 2).