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ORIGINAL ARTICLE
Year : 2014  |  Volume : 10  |  Issue : 2  |  Page : 342-346

To analyze the impact of intracavitary brachytherapy as boost radiation after external beam radiotherapy in carcinoma of the external auditory canal and middle ear: A retrospective analysis


Department of Radiotherapy, Dr. D K Gosavi Memorial, Siddhivinayak Ganpati Cancer Hospital, Miraj, Maharashtra, India

Date of Web Publication14-Jul-2014

Correspondence Address:
Dinesh K Badakh
Dr. D K Gosavi Memorial, Siddhivinayak Ganpati Cancer Hospital, Miraj-Sangli Road, Miraj, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.136624

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 > Abstract 

Purpose: The purpose of this study was to analyze the impact of intra-cavitary brachytherapy (ICBT) as boost radiation after external beam radiotherapy (EBRT) in carcinoma of the external auditory canal and middle ear (EACMA): A retrospective analysis.
Materials and Methods: A retrospective study of 18 patients with carcinoma of the EACMA who were treated with a curative intent from the year 1998 to 2010 was carried out. The age of the patients ranged from 25 years to 67 years. There were 11 male patients (61.1%) and 7 female patients (38.9%). A total of 15 (88.2%) patients were treated with curative radiation alone after a biopsy and two patients received post-operative radiation therapy. The patients were initially treated with EBRT with cobalt 60 machine up to 60-64 Gy. In our department, all the patients who were technically suitable for ICBT received an ICBT boost.
Results: The overall survival (OS) in these patients ranged from 7 months to 151 months (9 out of 17 patients, no evidence of disease 53%). The OS in patients treated with a combination of EBRT with ICBT was (8 out of 11) 72.7%, P value statistically significant (P value: 0.0024). The multivariate analysis shows statistically significant difference only for patients who got an ICBT boost (P Value: 0.020).
Conclusion: ICBT as a boost after EBRT has got a positive impact on the OS. In conclusion, our results demonstrate that radical radiation therapy (EBRT and ICBT) is the treatment of choice for stage T2, carcinoma of EACMA.

 > Abstract in Chinese 

回顾性分析外耳道和中耳癌外照射放疗后腔内放疗作为补充放疗的影响
摘要
目的:本研究回顾性分析腔内近距离放射治疗(ICBT)在外耳道和中耳癌(EACMA)中作为外放射治疗(EBRT)的补充放疗的影响。
材料与方法:对1998至2010年间18例EACMA患者进行了一项回顾性研究。患者的年龄介于25岁至67岁。男11例(61.1%),女性7例(38.9%)。总共有15例(88.2%)患者活检后进行单纯放疗,2例接受术后放射治疗。患者最初用钴60机进行外放疗,剂量60~64Gy。所有患者中适用于腔内放疗的均接受了补充腔内放疗。
结果:本研究患者生存时间从7个月到151个月(17例患者中有9例,没有复发的证据,占53%)。外放疗结合腔内放疗的OS为(8/11)72.7%,P值具统计学意义(P值:0.0024)。多因素分析显示仅腔内放疗补充的患者具有统计学显著性差异(P=0.020)。
结论:腔内放疗可作为外放疗的补充,延长患者生存时间,根治性放射治疗(EBRT和ICBT)是T2期EACMA的治疗选择。
关键词:近距离放射治疗,癌,外耳道,中耳,辐射


Keywords: Brachytherapy, carcinoma, external auditory canal, middle ear, radiation


How to cite this article:
Badakh DK, Grover AH. To analyze the impact of intracavitary brachytherapy as boost radiation after external beam radiotherapy in carcinoma of the external auditory canal and middle ear: A retrospective analysis. J Can Res Ther 2014;10:342-6

How to cite this URL:
Badakh DK, Grover AH. To analyze the impact of intracavitary brachytherapy as boost radiation after external beam radiotherapy in carcinoma of the external auditory canal and middle ear: A retrospective analysis. J Can Res Ther [serial online] 2014 [cited 2019 Sep 20];10:342-6. Available from: http://www.cancerjournal.net/text.asp?2014/10/2/342/136624


 > Introduction Top


The carcinoma of external auditory canal and middle ear (EACMA) is a rare disease. The reported prevalence of 1/1 million persons. [1] The role of radiation therapy as the primary modality in these tumors is still not well-established. [2] Most studies still recommend surgery followed by radiation therapy as the standard of care for cancers of EACMA. [1],[2],[3],[4],[5] In most studies, the incidence of surgical cut margin positive disease is very high (45% to 50%). The patients where a complete surgery is not possible have a poorer survival. In the present study, we performed a retrospective analysis of 18 patients of EACMA who were treated with a curative intent. Patients were treated with either surgery followed by radiation therapy or radical radiation therapy alone with or without intra-cavitary brachytherapy (ICBT). In our series, only two patients had undergone curative surgical approach and received post-operative radiation. The other patients were treated with radical external beam radiation therapy (EBRT) followed by ICBT wherever it was technically possible. Our interest was to analyze the effect of ICBT as boost radiation following EBRT and observe its effect on survival outcome. It was possible to give a higher total radiation dose with the ICBT technique. This is one of the largest series of ICBT of the EACMA carcinoma patients.


 > Materials and methods Top


A retrospective analysis of patients of carcinoma of the EACMA treated from the year 1998 to 2010, in the Department of Radiation Oncology was carried out. During this time period 18 patients were found suitable for analysis. The patients who presented with recurrence of disease after previous radiation treatment or surgery were excluded from the analysis. The patients with histology of either squamous cell carcinoma, adenoid cystic carcinoma or adenocarcinoma were considered for the study. Sarcomas, lymphomas, and melanomas were not considered for analysis. All the patients who had skin carcinoma of pinna were also excluded. The patients who had EACMA, who were treated with a palliative intent were also excluded.

The age of the patients ranged from 25 years to 67 years (Median age 51.50 years). There were 11 male patients (61.1%) and 7 female patients (38.9%). One patient had histological diagnosis of adenoid cystic carcinoma, but received incomplete radiation to the dose of 8 Gy due to non-compliance and so was not taken for further analysis. Out of the remaining 17 patients, 15 (88.2%) patients had squamous cell carcinoma and two patients had adenocarcinoma. The details of patient characteristics and treatment are given in [Table 1]. A total of 15 (88.2%) patients were treated with radical radiation alone after a biopsy, and two patients were treated with post-operative radiation therapy. The patients who were treated with post-operative radiation received only EBRT and no ICBT. The EBRT dose was 54 Gy and 56 Gy in the two post-operative patients.
Table 1: Patient characteristics

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The staging of these patients was carried out with the aid of clinical examination, computed tomography (CT) scan and as per the pathology report in patients where surgery was done. The T staging was carried out as per Arriaga's classification (1); the N staging was the absence of nodes (N0) or presence of nodes (N1). The M staging was the absence of distant metastasis (M0) or presence of distant metastasis (M1).

The two patients who underwent prior surgery, one of them had a wide excision craniotomy carried out with negative surgical margins. The second patient had a wide excision of the external auditory canal and parotidectomy carried out also with negative surgical margins.

The patients were initially treated with EBRT with a single lateral field up to 40 Gy and then they were treated with two oblique wedge paired fields to a dose of 20-24 Gy. Two dimensional CT based planning was done for all patients. The EBRT fields covered the tumor and included the entire ear, ipsilateral parotid, and mastoid bone that is included both the pre auricular and post-auricular nodes. The level III and IV neck nodes were not included in the treatment field. The EBRT dose was in the range of 54 Gy to 66 Gy (median dose 60 Gy) with a daily fraction size of 1.8-2 Gy. All patients were treated on Cobalt 60 machine.

In our department, all patients who were technically suitable for ICBT were treated with ICBT. A total of 6 patients did not receive ICBT for the following reasons. Two were post-operative patients, one patient had pinna involved, in one patient the temporal lobe of the brain was involved, one patient had a base of skull involvement, in one patient cavity was totally blocked. The rest 11 patients were treated with ICBT. ICBT treatment length of 1 cm to 3.5 cm, dose: 7.5 Gy to 12.5 Gy (average 10 Gy) fraction sizes of 2.5-3 Gy treated twice daily, with high dose rate (HDR) brachytherapy machine. The ICBT dose was prescribed at 7 mm from the center of the catheter. The patients were treated with ICBT 3-4 weeks after completion of EBRT, when the acute reactions of EBRT had subsided. A single brachytherapy catheter was put in the ear cavity and it was secured in a central position. The length of treatment varied because some patients had perforated tympanic membrane due to disease and some patients did not.

The follow-up of the patients was from 7 months to 151 months (median 27 months). The follow-up patient was done from the records in charts and home visit by the social worker. The statistical analysis was performed by SPSS software (Version 10). The overall survival (OS) rates were calculated by Kaplan-Meier method and were measured from the 1 st day of radiotherapy. Differences between the groups were estimated using the log-rank test. Multivariate analysis was performed using the Cox regression model. A probability level of 0.05 was chosen for statistical significance.


 > Results Top


We have done this retrospective analysis of EACMA carcinoma patients from the year 1998 to 2010. We analyzed all patients who were treated with an intention to cure. As per the department policy patients treated with curative radiation as the primary modality of treatment were treated with EBRT and ICBT except if ICBT was not possible because of some reasons (outlined earlier) or it was technically not feasible [Table 1].
Table 2: Multivariate cox regression analysis variables in the equation

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We analyzed different patient related, tumor related and treatment related factors which could possibly have an impact on survival. The OS in these patients ranged from 7 months to 151 months (9 out of 17 patients NED 53%). Median survival was not reached. Total 8 (8 out of 17 patients died 47%) events occurred [Figure 1]. The seven patients died within 24 months of follow-up and one died at 27 months.
Figure 1: Overall survival

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The patient related factors analyzed were age and sex of the patient. Statistically no significant difference in survival was seen as per the sex of the patient or age of the patient (age < 50 or ≥ 50). The tumor related factor analyzed was the T stage. The stage wise analysis of patients was done, the stage distribution was as follows (T1: 0 [0%], T2: 7 [41%], T3: 5 [29.5%], T4: 5 [29.5%]). All the patients were node negative and had no evidence of distant metastasis. The T2 stage patients had better survival than T3 and T4 stage patients; however, there was statistically no significant difference in survival as per the T stage of the disease; the patient number in our study was less [Figure 2].
Figure 2: Graph for overall survival according to tumor(T) stage

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The treatment related factors studied were surgery and EBRT, EBRT alone and EBRT with ICBT. There was no difference in survival of patients treated with radiation alone or surgery followed by radiation [Figure 3]. We have only two patients in the surgery followed by radiation group.
Figure 3: Survival graph in patients treated with surgery followed by post-operative radiation alone

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The only factor made a statistically significant impact on survival was whether they received ICBT or no ICBT. The median survival for EBRT and ICBT group has not been reached. The OS in patients treated with EBRT and ICBT was (8 out of 11) 72.7%. The log rank test is showing P value 0f 0.0024, and is statistically significant [Figure 4]. The multivariate analysis shows statistically significant difference only for brachytherapy ICBT (P Value: 0.020) as shown in [Table 2].
Figure 4: Survival graph for groups surgery and external beam radiation therapy, EBRT alone EBRT and intra-cavitary brachytherapy

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There was no Grade 3 or 4 acute or late toxicities observed. There was no osteoradionecrosis seen in any of the patients. The only problem observed was fungal infection in two of the patients, who required surgical cleaning of the ear and fluconazole treatment. It took around 4-6 weeks for this infection to get resolved. We had not done any audiometric tests for our patients pre-radiation or post-radiation, so are not able to comment about hearing loss.


 > Discussion Top


The reported prevalence of carcinoma of EACMA is 1/1 million persons. [1] As the disease is rare, most of the studies of EACMA carcinoma are retrospective. Different staging or classifications have been used (Stell's, Arriagas, Shih and Crabtree) by investigators, thus making it difficult to analyze and compare different treatment results.

We have classified or staged our patients as per the Arriaga's classification. We treated all our patients who were not operated, with primary radiation therapy (EBRT and ICBT). The median OS in patients treated has still not been reached (9 out of 17 patients alive, OS 53%). The patients with stage T2, T3 and T4, the OS is (5 out of 7) 70%, (2 out of 5) 40% and (2 out of 5) 40% respectively. The OS in patients treated with EBRT and ICBT was (8 out of 11) 72.7%. Whether patients were treated or not treated with ICBT was the only statistically significant factor in multivariate analysis.

In our analysis, it was seen that patients of EACMA carcinoma of stage T2 had a very good survival with primary radiation therapy (EBRT and ICBT). Even stage T3 and T4 patients had 40% survival. Our study is different in a way that we routinely used ICBT as boost technique wherever it was technically feasible.

Surgical treatment followed by post-operative radiation is considered the standard of care for carcinoma of EACMA patients. [1],[2],[3],[4],[5],[6],[7],[8],[9] In a study by Ogawa et al., surgery was performed in 53 patients, in this study 23 patients had negative surgical margins (43.4%) and 30 patients had microscopic surgical margins positive or gross residual disease left behind (56.6%), [1] other studies also showed a high incidence of surgical margin positive rate, [2] and in some the incidence was even 100%. [4] The study recently published on treatment of EACMA carcinoma patients treated post-operatively with intensity modulated radiotherapy had positive surgical margin in five patients (45%). [5] From all these studies it is clear that Surgical Margin Positive rate is from 45% to 100%.

The studies which recommended surgery followed by radiation therapy as the standard of care had a high incidence of surgical margin positive disease. They also concluded that patients with surgical margin positive disease had a poor OS as compared to negative surgical margin disease in cases of carcinoma of EACMA. [1],[2],[5],[9]

In a recent study by Chen et al., [5] he has emphasized the importance of attaining local control as local recurrence is the predominant pattern of failure in these patients. Thus ICBT can serve as a useful means to deliver a higher dose and enhance local control.

Some studies concluded and recommended treatment with radical radiation in early stage T1 disease (Stell's classification) of the carcinoma of EACMA to be effective. [1],[3] Our results show that T2 stage carcinoma of EACMA can be treated primarily with EBRT and ICBT without surgery.

For Stage T3 and T4 of EACMA carcinoma most of the studies recommended surgical excision followed by radiation therapy as standard treatment. The problem is that of a high surgical margin positive rate in these patients, which ranged from 45% to 100%. We only had five patients in stage T3 and five patients in stage T4, for both these stages the OS was 40%. The 5 year disease free survival rate in Ogawa et al., study was 55% for T3 and 27% for T4 stage disease. [1] In the study by Pfreundner et al., 5 year survival rate for T3 tumors was 50% and T4 stage 41%. Others also reported similar results. [7]

In our study, the difference is that of giving an ICBT boost radiation to the patients after EBRT, wherever technically feasible, when receiving primarily curative radiation treatment. The OS in patients treated with EBRT and ICBT was (8 out of 11) 72.7%. We think that the reason for such good results was because we were able to give a fairly high dose and a good patient selection. These patients effectively received 60-64 Gy EBRT followed by ICBT boost 7.5 Gy to 12.5 Gy with HDR machine. The limitation with EBRT is that it is difficult to deliver high doses to the temporal bone due to proximity to the brain thus ICBT is a good way to escalate dose while sparing the critical structures. So, we were able to treat patients with higher radiation doses. The ICBT treatment finished within 2-3 days and spared the surrounding normal tissues, this may have resulted in increased local control rate and OS with minimal toxicity. Ogawa et al., in their study treated three patients with HDR ICBT in addition to EBRT. [1] After 30-50 Gy EBRT, HDR ICBT 15-42 Gy was delivered as boost treatment with a single dose of 3 Gy at 5-7 mm applicator distance with five fractions (one patient with a T2 tumor) or 10 fractions/week (two patients with T1 tumors). In their analysis all three patients were locally controlled (100%) without serious late complications.

Pfreundner et al., in their study also treated three patients of post-operative EBRT with brachytherapy boost treatment. [2] In these three patients, two were locally controlled (66.6%). They also studied four patients with recurrent disease after surgery and radiotherapy. The brachytherapy was used as salvage treatment. In these four patients two failed locally, one in the neck node and one patient was controlled and disease free, so local control rate was 50% (2 out of 4 patients).

Both the above two studies shows that ICBT boost increases local control rate and survival of the patients. Similar findings are seen in our patients also.


 > Conclusion Top


ICBT as boost after EBRT is feasible and have a positive impact on OS. In conclusion, our results demonstrate that radical radiation therapy (EBRT and ICBT) is the treatment of choice for stage T2 carcinoma of EACMA. For stage T3 and T4 if negative surgical margins are not achievable or if surgical expertise is not available than primary radiation therapy (EBRT and ICBT) gives a reasonable OS. However, this was a retrospective study comprising of a small number of patients. In this rare cancer, a multi-centric trial with large number of patients is needed to confirm our results.

 
 > References Top

1.Ogawa K, Nakamura K, Hatano K, Uno T, Fuwa N, Itami J, et al. Treatment and prognosis of squamous cell carcinoma of the external auditory canal and middle ear: A multi-institutional retrospective review of 87 patients. Int J Radiat Oncol Biol Phys 2007;68:1326-34.  Back to cited text no. 1
    
2.Pfreundner L, Schwager K, Willner J, Baier K, Bratengeier K, Brunner FX, et al. Carcinoma of the external auditory canal and middle ear. Int J Radiat Oncol Biol Phys 1999;44:777-88.  Back to cited text no. 2
    
3.Hashi N, Shirato H, Omatsu T, Kagei K, Nishioka T, Hashimoto S, et al. The role of radiotherapy in treating squamous cell carcinoma of the external auditory canal, especially in early stages of disease. Radiother Oncol 2000;56:221-5.  Back to cited text no. 3
    
4.Korzeniowski S, Pszon J. The results of radiotherapy of cancer of the middle ear. Int J Radiat Oncol Biol Phys 1990;18:631-3.  Back to cited text no. 4
    
5.Chen WY, Kuo SH, Chen YH, Lu SH, Tsai CL, Cheng JC, et al. Postoperative intensity-modulated radiotherapy for squamous cell carcinoma of the external auditory canal and middle ear: Treatment outcomes, marginal misses, and perspective on target delineation. Int J Radiat Oncol Biol Phys 2012;82:1485-93.  Back to cited text no. 5
    
6.Hahn SS, Kim JA, Goodchild N, Constable WC. Carcinoma of the middle ear and external auditory canal. Int J Radiat Oncol Biol Phys 1983;9:1003-7.  Back to cited text no. 6
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7.Austin JR, Stewart KL, Fawzi N. Squamous cell carcinoma of the external auditory canal. Therapeutic prognosis based on a proposed staging system. Arch Otolaryngol Head Neck Surg 1994;120:1228-32.  Back to cited text no. 7
    
8.Testa JR, Fukuda Y, Kowalski LP. Prognostic factors in carcinoma of the external auditory canal. Arch Otolaryngol Head Neck Surg 1997;123:720-4.  Back to cited text no. 8
    
9.Nyrop M, Grøntved A. Cancer of the external auditory canal. Arch Otolaryngol Head Neck Surg 2002;128:834-7.  Back to cited text no. 9
    


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