Japanese Journal of Clinical Oncology Advance Access originally published online on October 4, 2006
Japanese Journal of Clinical Oncology 2006 36(11):681-687; doi:10.1093/jjco/hyl099
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© 2006 Foundation for Promotion of Cancer Research
Long-term Functional Outcome of Brachytherapy for Carcinoma of the Mobile Tongue: Focus on the Atrophic Change of Irradiated Tongue
1 Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka
2 Department of Clinical Radiology, Kitakyushu Municipal Medical Center, Kitakyushu, Fukuoka
3 Department of Oral Maxillofascial Radiology, Faculty of Dentistry, Kyushu University, Fukuoka
4 Department of Medical Information Science, Kyushu University Hospital, Fukuoka
5 Department of Radiologic Technology, School of Health Sciences, Kyushu University, Fukuoka, Japan
For reprints and all correspondence: Yusuke Urashima, Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan. E-mail: urash{at}radiol.med.kyushu-u.ac.jp
Received May 2, 2006; accepted July 8, 2006
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Abstract |
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 TOP Abstract INTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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OBJECTIVE: To assess tongue atrophy and long-term functional outcome of mobile tongue cancer patients after interstitial radiotherapy.
METHODS: Of 493 patients whose squamous cell carcinoma of the mobile tongue had been treated with low dose rate brachytherapy, there were 57 patients evaluated between July 2002 and April 2004 whose tongue had not been modified by surgical procedures and who had no primary recurrence. The median time from treatment to evaluation was 96 months (range: 9–214 months). Almost all of the patients belonged to the early stage tongue cancer (T1/T2/T3/T4=30:24:3:0), and all had received interstitial radiotherapy with a single-plane implant. To evaluate the deformity of the tongue, we used a grading system that classified the atrophic changes of the tongue into four categories (G0–G3).
RESULTS: Thirty-nine patients (70%) showed mild tongue hemiatrophy (G1 or G2) in the irradiated side. However, no patients showed severe atrophy where the tongue cannot be made to protrude beyond the incisors (G3). The length of time after brachytherapy was >72 months and the age of the patients at brachytherapy had the same statistical significance (P=0.0366). As for functional outcome, understandability of speech and a normal diet were preserved for almost all patients.
CONCLUSION: The progression of atrophic change in the irradiated tongue occurred over a long term after brachytherapy. However, most patients could maintain their activities of daily life without severe restriction.
Key Words: tongue cancer • brachytherapy • tongue atrophy • functional outcome • QOL
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INTRODUCTION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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Brachytherapy has played an important role in the treatment of oral tongue carcinoma not only because of its good outcome but because it preserves the structure and function of the tongue. Although many investigators have supported these advantages of brachytherapy (1–6), some reports documented its severe complications, such as osteoradionecrosis, soft tissue necrosis and ulceration. In addition, tongue hemiatrophy after brachytherapy is considered relatively common (7,8). However, only a few reports have studied the relationship between the objective evaluation of tongue atrophy and the function of the tongue (8).
In this study, we investigated tongue atrophy and functional outcome in patients with tongue cancer after brachytherapy, particularly in patients who were followed up for a long period. In addition, we examined the factors influencing the degree of atrophic change of the irradiated tongue.
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PATIENTS AND METHODS |
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Patient Characteristics and Selection
From 1978 to 2003, 493 patients with tongue cancer were treated with low dose rate brachytherapy at the Department of Radiology of Kyushu University Hospital. To examine the effect of brachytherapy on tongue atrophy, the following eligibility criteria were used in this study: (a) brachytherapy performed with or without external radiotherapy; (b) no modification to the tongue by surgical procedures such as partial resection or excision; (d) no cervical lymph node or distant metastasis present at the time of initial radiotherapy; (e) no primary recurrence.
Of the 493 patients, we evaluated 57 patients between July 2002 and April 2004, who visited our out patient clinic and met all of the criteria. The median time from treatment to evaluation was 96 months (range: 9–214 months). There were 23 men and 34 women. Their median age was 57 (range: 22–84 years) at initial treatment. Histologically, all cases were squamous cell carcinoma. The UICC TNM classification of 2002 identified 30 patients as T1, 24 as T2 and three as T3.
Treatment
Interstitial radiotherapy was performed with radium-226 needles in 28 patients, cesium-137 needles in 23 patients and iridium-192 hairpins in six patients. Radiation doses were delivered by the implantation of radioactive sources and doses reached 70 Gy/week, according to the Paterson–Parker dosage system. All the patients were treated with single-plane implants.
Of the 57 patients, 11 received external radiotherapy prior to interstitial radiotherapy. External radiotherapy was given with megavoltage (4–6 MV) irradiation from a linear accelerator. The primary tumor and the upper neck were treated with two upper opposite parallel portals. These fields were treated with a dose of 1.5–2 Gy/fraction/day, 5 days/week, to a median total dose of 30 Gy (range: 10–30.4 Gy). The dose of interstitial radiotherapy was not modified except for one patient whose dose was reduced to 50 Gy because of marked shrinkage of the tumor after external irradiation.
Chemotherapy was combined with radiotherapy in 25 patients, of whom 19 were treated with a 5-fluorouracil-based regimen, four with bleomycin alone and two with cisplatin and tegafur uracil.
The only late complications of brachytherapy were bone exposure in seven patients and ulceration in 11 patients.
Among the 57 patients, 13 received radical neck dissection because of their cervical failure.
Grading of the Tongue Atrophy
To evaluate the tongue deformities, we used the grading system proposed by Yoshioka et al. (8). This system, the details of which are shown in Fig. 1, classifies the atrophic changes of the tongue into four categories (G0–G3).
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Evaluation of Functional Outcome
Functional outcome was evaluated based on the patient's ability to eat a regular diet and the understandability of his or her speech. All 57 patients in this study were interviewed by the authors of this study with the use of a questionnaire based on a performance status scale for head and neck cancer patients (Table 1) (9).
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Statistical Methods
To investigate several factors that may have influenced tongue atrophy, we compared the G0 group (n=17) and the G1–2 group (n=40). The
2 test was used to compare subgroups that were divided according to the existence or nonexistence of tongue atrophy. In addition, prognostic variables for the existence of tongue atrophy were tested for independent significance by stepwise logistic regression analysis. In addition, Spearman's rank correlation coefficient was used to analyse the relationship between the grade of tongue atrophy and factors.
The statistical software program StatView, version 5.0 (SAS Institute Inc., Cary, NC) and SAS release 8.2 (SAS Institute Inc., Cary, NC) were used for the statistical analyses.
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RESULTS |
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Tongue Atrophy Grading Results
In the grading of the tongue atrophy, 18 patients were classified as G0, 20 as G1 and 19 as G2. No patients were classified as G3.
Figure 2 shows the relationship between the grade of tongue atrophy and the length of time after brachytherapy. Although G2 atrophy was seen even within 10 months after brachytherapy in one patient, the atrophic change in the irradiated tongue tended to progress over the long term after brachytherapy. According to Spearman's rank correlation coefficient, there was a statistically significant relationship between the grade of tongue atrophy and the length of time after brachytherapy (P=0.0110, 
=0.334).
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Figure 3 shows the relationship between the grade of tongue atrophy and the age of the patients at brachytherapy. This analysis showed that the risk of tongue atrophy tended to increase in younger patients. According to the Spearman's rank correlation coefficient, there was also statistical significant relationship between the grade of tongue atrophy and the age of the patients at brachytherapy (P=0.0337,
=–0.284).
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As for the result of
2 test, differences were found in the age of the patients at brachytherapy (P=0.0387), in the existence of neck dissection (P=0.0471) and in the length of time after treatment (P=0.0243) (Table 2). Multivariate analysis also showed that the length of the time after brachytherapy was 
72 months and the age of the patients at brachytherapy had the same statistical significance (P=0.0366) (Table 3).
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Results of Evaluation of Functional Outcome
Table 4 shows the functional outcomes according to tongue atrophy. Almost all of the patients preserved the understandability of their speech and the normalcy of their diet. Full marks were given to 56 patients (98%) for speech understandability and to 53 patients (93%) for dietary normalcy. Of the five patients who scored less than 80 points in normalcy of diet, four scored 50 points because of a loss of teeth with aging and one patient scored 70 points because of a tongue deformity after radiation-induced ulceration.
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DISCUSSION |
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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It has generally been accepted that brachytherapy for the treatment of early tongue cancer is an excellent means of achieving local control (1–6). Although many articles have investigated the control rate of tongue cancer, surprisingly few have referred to long-term tongue atrophy and functional outcome of radiation for mobile tongue.
A few reports referred to tongue atrophy (7,8,10,11). Among them, Yoshioka et al. documented that tongue atrophy occurred in 71% of patients and severe atrophy was seen in only one patient, based on a survey of 49 mobile tongue cancer patients treated with low dose rate or high dose rate brachytherapy (8). In our study, tongue atrophy occurred in 39 (70%) of 57 patients, so the rate of tongue atrophy was almost identical to theirs.
Regarding other head and neck malignancies with external radiotherapy, Wu et al. showed that the rate of tongue atrophy was 54.8%, after a mean follow-up period of 8.5 years (2–20 years), among 31 patients with nasopharyngeal carcinoma who had been treated with external radiotherapy (10). Puthawala et al. studied 70 patients with cancer at the base of the tongue after they had been treated with primary radiotherapy, and also reported two cases of tongue atrophy as a complication after radiation (11). According to their report, unilateral tongue atrophy was observed in two patients, 2 and 3 years after treatment.
Considering those reports, it is evident that atrophy of the tongue occurs after radiotherapy. However, there are few papers on the relationship between the degree of tongue atrophy and the length of time after treatment. As shown in Fig. 2, the longer the follow-up period was, the higher the grade of tongue atrophy seemed to become. In addition, the length of time after treatment was a significant factor influencing the degree of atrophic change of the irradiated tongue in our study. Therefore, we believe that the degree of tongue atrophy tended to correlate with the length of time after brachytherapy.
The mechanism of tongue atrophy may resemble the process of muscle injury after radiotherapy. Animal research on the effects of radiation on muscle has focused on the histopathologic features of acute myositis and late muscle atrophy (12,13). Some authors studied cytokines in injured muscle, as well as the late proliferation of fibroblasts and the synthesis of matrix proteins, after radiotherapy (14,15). In humans, late muscle injury evolves over several years after fractionated external beam radiotherapy and, on the basis of animal study findings, is most likely a result of the gradual loss of vascular supply (16). These data support the clinical evidence of the relationship that our study has found between the degree of tongue atrophy and the length of time after treatment.
Another reason for tongue atrophy may be hypoglossal nerve injury leading to tongue atrophy. King et al. studied 12 nasopharyngeal cancer patients and described the appearance of the tongue following radiation-induced neuropathy of the hypoglossal nerve (17). In our study, the doses of external radiotherapy were no more than 30 Gy, not enough to cause cranial nerve atrophy according to previously published reports (18,19) (62.5–100 Gy, 6000–8000 R). However, in almost all cases, the minimum tumor dose of brachytherapy reached as high as 70 Gy. Therefore, it was possible that the implanted radioactive sources directly caused hypoglossal denervation.
Another factor that could influence the hypoglossal nerve is hypoglossal paralysis, which has been reported as a complication of radical neck dissection (20,21). In our study, 13 patients received radical neck dissection for their cervical failure. The possibility can not completely be excluded that radical neck dissection injured the hypoglossal nerve in those 13 patients. However, as shown Table 3, the statistical analysis showed no significant relation between the existence of tongue atrophy and the existence of neck dissection. According to the published report, the frequency of unintentional injury to the nerves has been reported to be less than 5% (21).
As for the relationship between the grade of tongue atrophy and the age of the patients at brachytherapy, the result of this study showed that the risk of tongue atrophy tended to increase in younger patients. Although there was no data about the volume of the tongue in our study, it was probable that the radiation-induced tongue atrophy varied depending on the amount of the muscle of the tongue. As for the age-related atrophy of the tongue, Bässler studied autopsy materials of 170 tongues and reported that an age-related progressive increase of fatty tissue occurred with atrophy of the muscle fibers in the musculature of the tongue (22).
As for complication history, 18 of the 57 patients had tongue ulcer or bone exposure. In this study, the statistical analysis showed no significant relation between history of complication and grade of atrophy. However, severe tongue ulcer may be a cause of tongue deformity. Further investigation should be made to reveal the relationship between these factors and the events.
As for tumors themselves as an influencing factor, almost all patients in this study belonged to T1 or T2 and all the tongue tumors were thin enough to be treated with single-plane implantation. These tumor characteristics might be a reason why the T-category did not appear to influence tongue atrophy in this study. Yoshioka et al. reported that the T-category tended to increase with the tongue atrophy grade, but they found no statistical significance between grade of tongue atrophy and T-category (8).
The functional outcome for the patients was assessed with a questionnaire using a validated performance scale for head and neck cancer patients developed by List et al. (9). This scale, which has been used in many studies (23–27), seems to be specific for head and neck cancer patients, and it can discriminate between different levels of functioning. Although some patients did not score highly because of a loss of teeth with aging, most patients maintained good scores in this study.
The aim of the present study was to investigate tongue atrophy and functional outcome in patients with tongue cancer after brachytherapy, particularly in those who were followed up for a long period. As a result, the number of the analysed patients was 57 out of 496 patients who were treated with brachytherapy in our institute. Further investigation is certainly required in order to avoid possible bias.
In conclusion, atrophic change of the irradiated tongue tended to progress over the long term after brachytherapy and the risk of tongue atrophy tended to increase in younger patients.
These issues should be kept in mind in the treatment of tongue cancer patients, but the influence of tongue atrophy may be so subtle that most the patients can maintain their activities of daily life without severe restrictions.
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TOPAbstractINTRODUCTIONPATIENTS AND METHODSRESULTSDISCUSSIONReferences |
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