Volume 49, Issue 1 , Pages 50-52, January 2011
Incidence of second primary tumours in patients with squamous cell carcinoma of the tongue
Article Outline
Abstract
We retrospectively studied 329 patients with squamous cell carcinoma (SCC) of the tongue who were treated at The Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Head and Neck Surgery of Cancer Hospital during the past 25 years (1975–2000). The patients were followed up for more than 36 months, and 28 (9%) developed 29 second primary carcinomas. The characteristics of the index tumour including the clinical appearance (10% nodular, 8% ulcerated), the site (10% anterior, 9% posterior, and 6% lateral), the classification (13% T1, 9% T2), the stage (12% stage I, 11% stage II, and 7% stage III), the histological appearance (7% well-differentiated, 14% moderately differentiated, 36% poorly differentiated, and 2% unknown), and the type of treatment given (18% resection only, 4% radiation only, and 6% combined treatment) were recorded. Twenty-three of the 29 second primary lesions developed in the upper aerodigestive tract with the oesophagus the most common site (79%). During the follow-up period, 14 patients died from causes associated with the second primary lesion and 5 from unrelated causes, and 9 patients were still alive at the time of follow-up. The prognosis for patients who develop second primary lesions is poor.
Keywords: Second primary carcinoma, Tongue neoplasm, Squamous cell carcinoma, Head and neck cancers
Introduction
Second primary carcinomas that develop in patients with head and neck cancer are a challenge, and are partly responsible for our failure to improve overall survival.1, 2 In 1932, Warren and Gates defined the criteria for a second primary carcinoma.3 These, with modifications by Nikolaou et al.,4 stated that the tumour must present a definite histological picture of malignancy, each tumour (primary and second primary) must be separate, and the second primary must be ruled out as metastatic spread from the first cancer. The incidence of second primaries in patients with previous head and neck carcinomas ranges from 12%5 to 19%,6 and in a meta-analysis Haughey et al. reported 14.2% of second primary cancers among 40,287 patients.7
The aim of the present study was to describe the incidence and character of second primary lesions among patients with squamous cell carcinoma of the tongue.
Patients and methods
The study group comprised 329 patients who were first treated at the Chinese Academy of Medical Sciences, Peking Union Medical College, Department of Head and Neck Surgery, for SCC of the tongue, and subsequently developed a SPC for the 25 years. There were 192 men and 137 women, whose ages ranged from 22 to 96 years (median 53). The number who developed a second primary lesion was noted, and the characteristics of the index tumour including clinical appearance, site, classification, stage, histological appearance, and the type of treatment given were recorded. All tumours were staged using the 1997 American Joint Committee on Cancer/Union International Contre le Cancer (AJCC/UICC) criteria.8 The shortest period of follow-up for survivors was 3 years. The statistical analysis was aided by use of the Statistical Package for the Social Sciences version 11.5 for Windows (SPSS Inc., Chicago, IL).
Results
Of the 329 patients with SCC of the tongue, 28 developed 29 second primary tumours (9%). Of the 2 synchronous carcinomas, one was diagnosed at the same time as the SCC of the tongue, and the other within 6 months (Table 1). Poorly differentiated SCC was the most significantly common histological presentation in patients with second lesions (p
=0.005) (Table 2). Patients who were operated on developed significantly more second primary lesions than those treated by radiotherapy alone or given combined treatment (p=0.009).
Table 1. Details of the 329 patients. Data are number (%).
| Index tumour of the tongue | Second primary tumour (n=29 tumours in 28 patients) | |||
|---|---|---|---|---|
| Sex | ||||
| Male | 192 | (58) | 23 | (82) |
| Female | 137 | (42) | 5 | (18) |
| Age | ||||
| Range | 22–96 | 39–78 | ||
| Median | 53 | 56 | ||
| T stage | ||||
| T1 | 82 | (25) | 11 | (13) |
| T2 | 190 | (58) | 17 | (9) |
| T3 | 43 | (13) | 0 | 0 |
| T4 | 14 | (4) | 0 | 0 |
| TNM stage | ||||
| I | 76 | (23) | 9 | (12) |
| II | 93 | (28) | 10 | (11) |
| III | 135 | (41) | 9 | (7) |
| IV | 25 | (8) | 0 | 0 |
Table 2. Characteristics of the tumours. Data are number (%).
| Carcinoma of tongue (n=329) | Second primary tumour (n=29 lesions in 28 patients)a | |||
|---|---|---|---|---|
| Clinical appearance | ||||
| Nodular | 99 | (30) | 10 | (10) |
| Ulcerative | 230 | (70) | 18 | (8) |
| Site | ||||
| Anterior | 126 | (38) | 13 | (10) |
| Posterior | 76 | (23) | 7 | (9) |
| Lateral | 127 | (37) | 8 | (6) |
| Differentiation | ||||
| Good | 206 | (63) | 14 | (7) |
| Moderate | 59 | (18) | 8 | (14) |
| Poor | 14 | (4) | 5 | (36) |
| Unknown | 50 | (15) | 1 | (2) |
| Treatment | ||||
| Resection alone | 84 | (26) | 15 | (18) |
| Radiation alone | 59 | (18) | 2 | (3) |
| Combination | 186 | (57) | 11 | (6) |
a27 of the tumours were metachronous, and 2 synchronous. The median time interval between diagnosis of the two tumours was 101 months (range 17–266). |
Most of the second lesions (n=23, 79%) arose in the upper aerodigestive tract, the oesophagus being the most common site (n=9). This was followed by the nasopharynx (n=4), the lungs (n=3), the cheek (n=2), the upper gingivae (n=2), and the hypopharynx, oropharynx, and larynx (n=1 each). Sites outside the aerodigestive tract included the stomach, pancreas, liver, and bile ducts.
Nine patients were still alive at the end of the period of follow-up; 19 had died, 14 from causes related to the second primary lesion.
Discussion
Modern theories of carcinogenesis tie in with Slaughter's proposal of “field cancerisation”, so patients with oral cancer are at risk of developing second or multiple primary cancers within the upper aerodigestive tract.9, 10 The incidence of second primary lesions in SCC of the tongue has been reported to be between 12%11 and 21%.12 Our study reports a rate of 9% (28/329) among patients with index tumours of the tongue, which is comparable to that described by Bold et al. who found that the ratio of second primary tumours to carcinoma of the tongue was 8.8%.13 Most of the cases in our study (93%) were metachronous (27/29). This is comparable to the percentage found by Hsu et al., who reported that 88% of their cases were metachronous.11
Paradoxically, our data also show a decline in the incidence of second tumours in patients with more advanced stages of cancer, there being 12% of patients with stage I, 11% with stage II, and 7% with stage III cancer who developed second primary lesions. No patient with stage IV developed one. The picture was similar as far as classification was concerned, as our data showed that second primary cancers often develop in early lesions: T1 (13%) or T2 (9%) with none in T3 or T4 tumours. This could be because patients now survive longer with less advanced disease, which gives ample time for a second primary carcinoma to develop. Sessions et al. reported that patients with T1 tumours did better than those with T2, who also did better than those with T3 and T4.12
Our results showed that the incidence of second primary cancers was higher among poorly differentiated SCC (36%) than among well (7%) or moderately differentiated (14%) tumours, and this was significant. Among the three types of treatment, patients who had only resection for their primary SCC of the tongue had the most second primary lesions (18%). Although this is significant, it could be because patients with T1 and T2 tumours were more likely to be treated by operation alone.
Our study has shown that 9 patients (32%) survived for more than 3 years. Fourteen (50%) died of their second tumour, while 5 (18%) died of unrelated causes. Hsu et al. found that the survival of patients with SCC of the tongue and a second primary tumour was 50% at 3 years and 30% at 5 years.11
Of our second primary tumours, 79%were found in the upper aerodigestive tract and the oesophagus was the most common site, followed by the nasopharynx. We reported no existing premalignant conditions in the oesophagus in our patients. Petit et al. conducted biannual oesophageal endoscopy and found metachronous tumours in 3% of 1560 patients.14
We followed patients up for at least 5 years. They were reviewed every month for the first year postoperatively, every two months during the second year, 4-monthly during the third and fourth years, and 6-monthly thereafter. Inspection of the oral cavity allows detection of oral cancers and we also do nasopharyngeal endoscopy. Patients who present with symptoms such as haemoptysis, haematemesis, pain, or shortness of breath are also offered gastroscopy and flexible bronchcoscopy, which allows detection of small tumours of up to a few millimeters15 and is superior to chest radiographs in which lesions are visible only if they are at least 1–2cm in size. Chest radiographs and magnetic resonance images (MRI) of the head and neck are taken at the end of the first year. As the use of full body positron emission tomography (PET) for the early detection of a second cancer is questionable, it is used only after multidisciplinary discussions. Early detection of a second primary tumour allows a better prognosis.
The prognosis of a second primary tumour is usually poor, which is one reason why they are usually not detected until an advanced stage. They often develop in a head and neck region that has previously been treated, making further treatment difficult. In addition, treatment options for these patients are usually limited by the time they are diagnosed. Our 3-year survival was 33% (n=9), with the second-tumour-specific mortality at 50% (n=14).
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PII: S0266-4356(10)00008-2
doi:10.1016/j.bjoms.2010.01.005
© 2010 The British Association of Oral and Maxillofacial Surgeons. All rights reserved.
Volume 49, Issue 1 , Pages 50-52, January 2011
