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Research Article

Tongue cancer after primary radiotherapy for nasopharyngeal carcinoma: Three cases report and literature review

W. Mnejja¹, N. Fourati¹, W. Siala¹, L. Farhat¹, F. Elloumi¹, A. Ghorbel², M. Frikha³, J. Daoud¹

¹ Department of oncology radiotherapy Habib Bourguiba Hospital Sfax Tunisia

² Department of oto-rhino-laryngology Habib Bourguiba Hospital Sfax Tunisia

³ Department of oncology chemotherapy Habib Bourguiba Hospital Sfax Tunisia

Correponding author: Fourati Nejla, Email: nejla_fourati@yahoo.fr.

 

 

Citation: Mnejja W, Fourati N, Siala W, Farhat L, Elloumi F, Ghorbel A, Frikha M, Daoud J. Tongue cancer after primary radiotherapy for nasopharyngeal carcinoma: Three cases report and literature review. J Nasopharyng Carcinoma, 2014, 1(19): e19. doi:10.15383/jnpc.19.

Competing interests:The authors have declared that no competing interests exist.

Conflict of interest: None.

Copyright:image001.gif2014 By the Editorial Department of Journal of Nasopharyngeal Carcinoma. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

 

Abstract

Purpose: Radiation induced cancer is a significant problem that can alter long term survival and quality of life after radiotherapy for nasopharyngeal carcinoma (NPC). Reports detailing radio induced tongue cancer are few. The aim of this study was to analyze clinicopathologic characteristics, treatment outcomes of radio induced tongue cancer developing after successful primary radiotherapy for NPC.

Patients and methods: Between 1993 and 2010, 507 patients with non metastatic NPC were treated by radical radiotherapy (70-75Gy) to the nasopharynx and involved lymph nodes with or without chemotherapy. Follow up was performed to evaluate tumor control and to detect late toxicity. We found 9 cases (1.7%) of second malignant tumor with no evidence of primary disease recurrence. Three of these patients (0.6%) had tongue localization.

Results: The age of patients at the time of primary radiotherapy was 24, 38 and 47 years. All patients had no history of cigarette smoking and alcohol drinking. The latency between radiotherapy for NPC and the diagnosis of tongue cancer was 36, 39 and 230 months. The three histopathology types were well- or moderately differentiated squamous cell carcinoma. The second tongue cancer occurred at the tongue base in two cases and the junction between the oral and the tongue base in one case. After undergoing treatment for second malignant tumor, one patient had no evidence of disease and two patients had never achieved complete response tumor and were alive with uncontrolled loco-regional disease.

Conclusion: Radio-induced tongue cancer is an uncommon complication of external beam radiotherapy for nasopharyngeal carcinoma. The risk may increase with a long term follow up and improved survival. The treatment of this second tumor is not well codified and the prognosis is poor comparatively with primary tongue cancer. Long term follow after treatment for NPC is necessary for early detection of this late complication.

Keywords: Nasopharyngeal carcinoma; Tongue cancer; Radiation induced carcinoma

 

Introduction

Nasopharyngeal Carcinoma (NPC) is a common head and neck cancer in Tunisia. It has a unique epidemiological and therapeutic aspect. Unlike other head and neck cancers which are mainly associated with cigarette smoking and alcohol drinking [1], NPC is however strongly associated with Epstein-Barr virus (EBV) [1,2, 3]. Environmental and genetic factors may also play a role in the genesis of NPC [4]. The treatment of NPC is based on external beam radiotherapy for the primary tumor and at cervical risk nodes. Recently concomitant chemotherapy using platinum agents has been used to patients with advanced NPC [5]. This use of radiation expose the risk of developing radio-induced malignancies especially in young patients cured of their NPC. It’s rare, but a critical side effect that can limit long term survival and alter quality of life. The most common histological type of second cancer is sarcoma [6, 7] and the most common localization is oral-pharyngeal [4]. In contrast, reports detailing radio-induced tongue cancer in patients treated for NPC are relatively few. The objectives of the current study were to report patients who developed tongue cancer after primary radiotherapy for NPC and to analyze clinicopathologic characteristics and treatment outcomes of these patients.

 

Patients and methods

Between 1993 and 2010, 507 patients with no disseminated NPC were treated by conventional radiotherapy. Chemotherapy was associated for patients with locally advanced NPC (T3-T4 and or node involvement). All patients underwent an oral examination and dental care before treatment.

Radiotherapy was delivered at a total dose of 70 to 75Gy to the nasopharynx and involved cervical lymph nodes. The primary tumor and adjacent nodal regions were irradiated with two lateral opposed cobalt 60 gamma rays at 40 Gy and the supraclavicular nodes were irradiated with a cervical field with spinal cord shielding. In this phase oral tongue was shielded and only the tongue base was irradiated. For the second phase of radiotherapy, the remaining dose was delivered via an anterior nasal field with dose specification at 7 cm, and a large cervical field with spinal cord shielding (Figure 1). The estimated radiation dose received by the different part of the tongue was calculated retrospectively by the treatment planification system (TPS-Varian-eclipse) for the patients with tongue radio induced cancer.

Follow-up was made every 3 months for the first 2 years, every 6 months for the next 3 years and then every year. Monitoring is based on physical examination and routine laboratory tests. MRI or CT scan of nasopharynx and cervical nodes was performed 6 months after treatment and than once a year to evaluate the tumor control and to detect late treatment toxicity.

Nine patients developed a second malignant tumor after successful treatment of NPC and 3 of them had a tongue cancer site. There was no evidence of nasopharyngeal recurrence. Eligibility for diagnosis of radio induced cancer was based on the criteria of Qian and coll. 1) a prior history of radiotherapy, 2) The secondary cancer must occur within the previously irradiated field, 3) histologic confirmation of the second malignancy and 4) a latency between irradiation and a second malignant tumor of at least 1 year [8].

 Figure 1a

 Figure1b

Figure 1. Lateral cervicofacial field (1a) and Nasal field (1b) GTV: Red, CTV: Magenta, Oral Tongue: Red, Tongue base: Green

Results

Patient’s characteristics radio induced tongue cancer

We estimated that the crude incidence of radio induced tongue cancer after radiotherapy for NPC was approximately 0.6%. Patient’s age at the time of primary radiotherapy was 24, 38 and 47 years. The latency between NPC radiotherapy and the diagnosis of tongue cancer was 36, 39 and 230 months. The three-tongue cancer histopathologies were well- or moderately well-differentiated squamous cell carcinoma. The second tongue cancer occurred at the tongue base in two cases and at the junction between the oral and the tongue base in one case. The characteristics of the patients were summarized in table 1.

The estimated retrospective dosimetry have shown that the mean doses received by the tongue base and the oral tongue were 65 Gy and 35 Gy.

 

 

Table 1: Patients characteristics at presentation of NPC

Patients

Age (years)

Sex

RT dose (Gy)

CT

TNM Classification

Histology

Number 1

38

M

70

PF (Cisplatin-Fluoracil)

T2bN2M0

UCNT

Number 2

47

M

70

PF (Cisplatin-Fluoracil)

T4N3M0

UCNT

Number 3

24

F

70

EP (Epirubicin-Cisplatin)

T3N2M0

UCNT

M: Male, F: Female, RT: Radiotherapy, CT: Chemotherapy, UCNT: undifferentiated carcinoma of nasopharyngeal type.

 

 

Treatment and outcomes

One of the three patients in our study has received combined radiotherapy and chemotherapy after undergoing complete resection surgery. One patient received palliative chemotherapy alone because non resecable lesion. The third patient proposed for chemotherapy but he refused treatment and received palliative care.

 After undergoing treatment for second malignant tumor, one patient has no evidence of disease and two patients were alive with uncontrolled loco-regional disease.

Patient and treatment characteristics for radio induced tongue cancer were summarized in table 2.

 

 

Table 2. Patients characteristics with radio-induced tongue cancer

Patients

Latency (months)

TNM Classification

Histology

Site

Treatment

Disease status

Survival after second cancer

Number 1

39

T2N0M0

WD SCC

Oral and base tongue junction

Surgery + RT + CT

NED

20 months

Number 2

36

T2N2bM0

MWD SCC

Tongue Base

CT

AWD

5 months

Number 3

230

T4 N0M0

 

MWD SCC

Tongue Base

Palliative care

AWD

7 months

WD SCC: well differentiated squamous cell carcinoma; MWD SCC: moderately well-differentiated squamous cell carcinoma; NED: no evidence of disease; AWD: alive with disease. RT: Radiotherapy, CT: Chemotherapy

 

 

Discussion

Radiotherapy alone or associated with chemotherapy is the most common treatment for NPC. It is responsible for multiple side effects [9]. Radio-induced cancers are the most feared late complication after treatment of NPC. We expose the two possible hypotheses for the development of tongue cancer after radiotherapy for NPC. Either the tongue cancer developed as a radiation-induced malignancy or as a second cancer. The tongue cancer is mainly correlated, as the other head and neck cancer, with tobacco smoking and high alcohol consumption [10, 11]. But NPC is associated with EBV infection, nitrosamines consumption and genetic factors. Since the tongue cancer and NPC do not share the same risk factors, the radiation carcinogenesis is more probable. On the other hand, tongue cancers had been reported after successful treatment for NPC but there were no case of NPC diagnosed after primitive tongue cancer [12].

The incidence of radio-induced cancer after treatment of NPC varies from 0.04 to 7% in the literature [4-13]. Malone and coll. [6] noted four (7%) radio-induced cancer after NPC radiotherapy treatment and the incidence for tongue localization was 1.8%. Teo and coll. [12] identified 19 radio-induced cancers out of 903 patients treated for NPC (2.1%) including 7 radio-induced tongue cancer (0.7%). In our study, nine patients developed second primary cancers (1.7%) with three cases of tongue cancer site (0.6%).

Radio-induced malignancies occurred with a mean latency of 10 to 15 years [14] but shorter interval between the two tumors was reported [15]. The average interval between first and second cancers after NPC irradiation was 15.5 years for Malone and coll. [6] and 5.33 years for Chen and coll. [4]. For tongue cancers, Teo and coll. [12] have reported a latency of 71.9 months (21-91 months). In our series, the mean interval between NPC radiotherapy and the development of tongue cancer was 101 months (range 36 to 230 months) which was compared with the literature latency period for the development of radiation-induced malignancies.

For the tumor site, the tongue cancers occurred mostly at the tongue base or the junction between the oral tongue and the tongue base which corresponded to the high dose region. The low radiation dose delivered to the oral tongue which is protected by tongue shields will also be associated with a significant risk of carcinogenesis after a longer latency period [12].

In the literature, very few papers reported on radiation induced tongue cancer after treatment of NPC and most of these are single institution  reviews  with  relatively  small  case numbers and short follow-up.   The   principle   cases  reported  in  the  literature  are summarized in table 3.

Table 3. Radio-induced tongue cancer after irradiation of NPC in the literature.

Authors

Nb of patients

Nb of cases of tongue cancer (incidence)

Mean age (years)

Sex (M/F)

Latency

Malone and coll. [6]

55

1 (1.8%)

64

M

11 years

Teo and coll. [12]

903

7 (0.7%)

42

2/5

71.9 months

Our series

507

3 (0.5%)

36

2/1

101 months

Sun and coll. [18] have reported the largest series of tongue cancer occurring after the treatment of NPC with 53 cases (data accessible only in abstract form). They identified 3 prognostic factors influencing survival of these patients: tumor size, clinical TNM stage at presentation and the interval between the two tumors. They have also compared, in a second study [19] the primitive tongue cancers (252 patients) with the radio-induced one (53 patients). They found that second tongue carcinoma after radiotherapy for NPC is likely to occur on the tongue dorsal with a lower rate of lymph node metastasis. But, it is associated with worse prognosis compared with primary tongue carcinoma. There were no significant differences in terms of age, sex, tumor size, cTNM stage, tumor differentiation and the rate of distant metastasis between the two groups. In their study, Teo and coll. [12] found that the stage distribution was comparable between the primitive tongue cancer and the radio-induced tongue cancer after NPC radiotherapy but the mean age and the sex ratio were significantly different. In fact, the risk of second tongue cancer after NPC radiotherapy was much higher in females than male and in younger patients under 40 years old at first diagnosis of NPC [4,11].

Prognosis is usually poor after second malignancies which occur in previously irradiated area. The treatment of these tumors was not well codified. Studies reporting the therapeutic manangment and outcomes of radio induced cancer in patients with NPC have been limited to case reports and a few small cases series, making it difficult to evaluate the best treatment strategy for this disease. In the absence of distant metastatic disease, surgery with complete resection could offer the best chance for long term survival. For patients with unresectable tumor, the alternative treatment was palliative chemotherapy. Reirradiation of second tumor has been reported as feasible in recent years. The high cumulative radiation dose may causes serious organ injury and be ineffective for an apparently radiation therapy– resistant tumor. Nevertheless, with the use of reirradiation, a durable control of disease has been reported [20].

 

Conclusion

Radiation induced tongue cancer is an uncommon complication of primary radiotherapy for NPC. Its incidence may increase with longer follow-up and as survival improves. Given the long latency between treatment for NPC and the development of a second malignancy tumor, careful and routine long-term follow-up is necessary for early detection of this late complication for patients who survive after treatment of NPC especially in young patients.

 To reduce the disease incidence, it is important that during modern three-dimensional conformal radiotherapy, planning with or without modulated intensity, the tongue should be spared as much as possible from high-dose irradiation without compromising the tumor covertures dose.

 

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