Aggressive multimodality management of locally advanced retromolar trigone tumors

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1 ORIGINAL ARTICLE Aggressive multimodality management of locally advanced retromolar trigone tumors Suryanarayana Deo S. V., MS, 1 * Nootan K. Shukla, MS, 1 Ashwin A. Kallianpur, MS, 1 Bidhu K. Mohanti, MD, 2 Sanjay P. Thulkar, MD 3 1 Department of Surgical Oncology, BRA-IRCH, All India Institute of Medical Science, New Delhi India, 2 Department of Radiation Oncology, BRA IRCH, All India Institute of Medical Science, New Delhi India, 3 Department of Radiodiagnosis, BRA IRCH, All India Institute of Medical Science, New Delhi India. Accepted 28 May 2012 Published online 21 August 2012 in Wiley Online Library (wileyonlinelibrary.com). DOI /hed ABSTRACT: Background. Retromolar trigone tumors are rare and aggressive malignancies. There is lack of quality evidence pertaining to their management due to the heterogeneity in treatment policies adopted. We retrospectively reviewed the patients of locally advanced retromolar trigone tumors treated with a standard and uniform multimodality management. Methods. A retrospective review of patients with locally advanced retromolar trigone tumors was performed and an analysis of clinicopathologic profile, treatment details, and survival outcomes was carried out. Results. Forty-two patients of locally advanced retromolar trigone tumors underwent the standard multimodality treatment. The majority of them presented with stage IVa disease. Margin negative resection could be achieved in 93% of patients. Histopathologically proven bone and node involvement was seen in 20 patients (47.6%) and 21 patients (50%), respectively. The 3-year disease-free and overall survival rates were 64% and 71%, respectively. Conclusions. Treatment of patients with locally advanced retromolar trigone tumors is challenging. However, good oncologic outcomes can be achieved by advocating an aggressive surgical approach with postoperative radiation therapy. VC 2012 Wiley Periodicals, Inc. Head Neck 35: , 2013 KEY WORDS: Retromolar trigone, tumor, oral cavity, radical surgery INTRODUCTION The retromolar trigone is a small but complex subsite of the oral cavity surrounded by vital anatomic areas. Retromolar trigone is a relatively rare subsite for oral cancer and the most frequent type of retromolar trigone tumor is squamous cell carcinoma. In general, tumors of the retromolar trigone have an aggressive biologic behavior due to predilection for early bone invasion, perineural and lymphatic spread, and infratemporal fossa invasion. In view of the rarity of the tumor and heterogeneity of treatment, there is limited literature available pertaining to retromolar trigone tumors. Various treatment modalities have been tried in the past including surgery, 1 3 radiotherapy, and combination therapy using chemoradiation. 4 There is controversy regarding the extent of surgery. Some advocate a radical surgical approach for every patient with retromolar trigone tumors, whereas some groups advocate a more limited surgical approach. 3 We present a review of locally advanced retromolar trigone tumors treated with a standard protocol using radical surgery and postoperative radiotherapy in a single center. *Corresponding author: Suryanarayana Deo S. V., MS, Department of Surgical Oncology, BRA IRCH, All India Institute of Medical Science, New Delhi India. svsdeo@yahoo.co.in This work was presented as an abstract at the 7th All India Students Conference on Science and Spirituality Conference on Internet Multimedia Systems Architecture and Application (IFHNOS 2010), Bangalore, India, December 15 17, MATERIALS AND METHODS A retrospective review of the prospectively maintained computerized database of patients with oral cancer treated in the Department of Surgical Oncology, All India Institute of Medical Sciences, New Delhi, was performed. Patients with locally advanced retromolar trigone tumors (stage III and IVa) treated between 2000 and 2009 were included for analysis. Patients with stage I and II retromolar trigone tumors and patients of tonsillar pillar, buccal, and palatal cancers with secondary involvement of the retromolar trigone were excluded. All patients had a clinical assessment for evaluation of the local extent of the spread to skin, bone, infratemporal fossa, and neck for nodal spread. A contrast-enhanced CT scan of the head and neck area was done in all patients and orthopantogram or 3D CT scan was used for assessment of mandibular involvement. Chest X-ray was also done to rule out lung metastasis. A punch or incision biopsy was done for histopathological confirmation of diagnosis. Disease was staged according to the 2009 American Joint Committee on Cancer staging system. The treatment approach for locally advanced retromolar trigone squamous cell carcinoma at our center has been consistent during the study period. All patients underwent radical surgery followed by postoperative radiotherapy. The surgical approach consisted of a lip split incision with an apron extension to the neck. After an optimal exposure of tumor, resection of the primary tumor was performed with a 1-cm tumor-free margin along with an en bloc hemimandibulectomy. Maxillary alveolectomy was performed in patients with tumors involving the upper HEAD & NECK DOI /HED SEPTEMBER

2 SURYANARAYANA DEO ET AL. TABLE 1. Stage distribution of locally advanced retromolar trigone tumors (7th edition of the American Joint Committee on Cancer). No. of patients by T classification N classification T1 T2 T3 T4a T4b N N N2a N2b N2c N Total Total no. of patients alveolus. All patients had an infratemporal fossa clearance including an en bloc resection of pterygoid muscles, inferior alveolar nerve, and pterygoid plexus. The soft tissue and mucosal defect was reconstructed using a standard pectoralis major myocutaneous flap. Mandibular reconstruction was not offered routinely. Mandibular reconstruction using titanium plates was performed in only 4 patients. A modified neck dissection sparing the spinal accessory nerve or radical neck dissection was performed in all the patients. Postoperative radiotherapy protocol consisted of external beam radiation 60 to 64 Gy in 30 to 32 fractions over a period of 5 to 6 weeks. All patients were followed every 3 months for the first 2 years, every 6 months for next 3 years, and annually thereafter. Patients were assessed clinically for evidence of locoregional recurrence, and radiological assessment was done when needed. All the locoregional relapses and second primaries were documented. A descriptive analysis of demography and clinicopathological features was performed and survival analysis was carried out using the Kaplan Meier method (SPSS v 15, IBM, Armonk, NY). RESULTS A total of 810 patients with oral cancer underwent operations between 2000 and Locally advanced retromolar trigone tumors constituted of 5.2% (42 of 810 patients) of all the oral cancers. There were 30 male and 12 female patients. Stage distribution is shown in Table 1. The mean age was 50 years (range, years). History of tobacco abuse was seen in 78% of patients (33 of 42). Twenty-two patients (52.3%) had trismus at presentation. Adjacent subsite involvement was seen in 64.2% of patients (27/42), predominantly to the buccal and alveolo-buccal areas. CT scans detected bone involvement in 17 patients (40%) preoperatively. However, pathological bone involvement was seen in 20 patients (47.6%). The sensitivity, specificity positive, and negative predictive value of CT for bone involvement in retromolar trigone tumors was 50%, 61.4%, 55.5%, and 76.9%, respectively. Table 2 shows the profile of resection and reconstruction procedures. Apart from the routine hemimandibulectomy, maxillary alveolectomy was performed in 14 patients. The majority had a type III modified neck dissection. Only 4 patients had mandibular reconstruction using a titanium plate. Forty patients (95.2%) received planned postoperative radiotherapy and radiotherapy was not given to 2 patients with a history of head and neck irradiation. There was no intraoperative complication noted. Postoperative complication was seen in 2 patients (1 had orocutaneous fistula and the other had flap dehiscence). Majority of the patients (90%) experienced postmandibulectomy and postradiation sequelae. Margin-negative resection was achieved in 93% patients (39 of 42), and only 3 patients had microscopic positive margins. The median number of lymph nodes dissected was 16 (range, 5 41), and histopathologically involved nodes were found in 21 of 42 patients (50%). The median number of histopathologically involved nodes was 2 (range, 1 8). The distributions of pathologically involved lymph nodes were as follows: only level I in 31% of patients (13 of 42), and level I and II in 19% of patients (8 of 42). The presence of skip nodal metastasis was seen in 7.1% of patients (3 of 42). As far as grade of tumor is concerned, 32 patients (76.2%) had well-differentiated tumors and 10 (23.8%) had moderately differentiated tumors. Pathologically proven mandibular involvement was seen in 20 patients (47.6%), including 5 patients (11.9%) with maxillary involvement. At a median follow-up of 20 months (range, 4 86 months), 10 patients (23.8%) had recurrence, 4 patients (9.5%) had local recurrence, 5 patients (11.9%) had regional recurrence, and 1 patient (2.4%) had both locoregional recurrence. Two patients with locoregional recurrence also had systemic relapse in the lungs. Three patients (7.1%) developed a second primary malignancy (2 tongue and 1 nasopharyngeal cancer). A total of 4 patients, including 2 with local recurrence and 2 with second primary, could be salvaged with re-surgery. The 3- year disease-free survival (Figure 1) was 64% and overall survival (Figure 2) was 71%. The 3-year disease-free survival in patients with pathological node negative and positive groups was 92% and 61%, respectively (Figure 3). On the study closing date, there were 34 patients (81%) alive with recent follow-up information. An additional 8 patients (19%) were lost to follow-up but contributed sufficient follow-up information to be included in the survival analysis (mean, months; median, 20 months). DISCUSSION Retromolar trigone tumors are a rare and aggressive group of oral cancers. Incidence of retromolar trigone TABLE 2. Profile of surgical procedures of patients with locally advanced retromolar trigone tumors. Procedure Resection profile Hemimandibulectomy 42 Maxillary alveolectomy 14 Infratemporal fossa clearance 42 Radical neck dissection 5 Modified neck dissection 37 Reconstruction profile Pectoralis major myocutaneous flap 40 Masseter flap 2 Titanium plate reconstruction 4 No. of patients 1270 HEAD & NECK DOI /HED SEPTEMBER 2013

3 MANAGEMENT OF LOCALLY ADVANCED RETROMOLAR TRIGONE TUMORS FIGURE 1. Represents the disease-free survival of patients with locally advanced retromolar trigone tumors. The 36-month diseasefree survival of 42 patients was 64%. Events ¼ 13. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] FIGURE 2. Represents the overall survival of patients with locally advanced retromolar trigone tumors. The 36-month survival of 42 patients was 71%. Events ¼ 9. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] varies between 15% and 26% of all squamous cell carcinomas involving the oral cavity in different series. 1 3 Retromolar trigone is a relatively small anatomic subsite in the oral cavity and some series have also included patients with secondarily involvement of retromolar trigone from tumors arising from adjoining areas like tonsillar, pillar, and buccal mucosa. 3 6 Owing to the rarity of disease, many of the previously published studies included both early and locally advanced tumors together for survival analysis. 2,7 9 In the current study, only tumors arising from the retromolar trigone were included, and retromolar trigone tumors constituted 5.2% of all oral cancers. In addition, only patients with stage III and IVa were included in the current study, and a standard treatment policy was applied to all the patients. Various imaging modalities can be used for mandibular assessment in oral cancer. A CT scan is one of the most common modalities used, and variable results of accuracy were reported in the literature. 3,10 12 Weisman et al 10 found that 33% of patients with histologically proven bone infiltration showed no radiological sign of bone invasion. In the review by Tsue et al, 11 34% of the mandibular specimens (11 of 32) demonstrated cancerous involvement, which was not detected radiologically. Lane et al, 12 in his series of 26 patients, reported 50% sensitivity, 91% specificity, and 61.1% negative predictive value of CT detecting mandibular invasion. The sensitivity, specificity, and negative predictive value of CT for bone involvement in retromolar trigone tumors in the current study was comparable to figures quoted in the literature. 12 FIGURE 3. Represents the disease-free survival of patients with node positive (N1) and node negative (N0) locally advanced retromolar trigone tumors. The 36-month and 60-month disease-free survival of 21 patients of node negative (N0) ¼ 92%. The 36-month and 60-month disease-free survival of 21 patients of node positivity (N1) ¼ 61% p ¼.014. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.] HEAD & NECK DOI /HED SEPTEMBER

4 SURYANARAYANA DEO ET AL. The low sensitivity and negative predictive value of CT for bone involvement in retromolar trigone tumors predicts that half of the patients can still present with histologic bone invasion despite no radiologic sign of bone invasion. The possible explanation of these suboptimal results may be due to the thick section studies (>5 mm) and the deficiency of high resolution bone algorithm on the retromolar trigone region. 12 As far as bone involvement is concerned Kowalski et al, 7 reported pathological mandibular involvement in 14% of 114 patients undergoing hemimandibulectomy. Hao et al 13 documented maxillary and mandibular involvement in 22% and 18%, respectively, of patients with retromolar trigone tumors undergoing mandibular resection. In the current study, pathologically mandibular and maxillary involvement was documented in 47.6% and 11.9%, respectively, probably due to a large number of locally advanced patients included for analysis. Because of the rarity of retromolar trigone tumors and the retrospective nature of the majority of the studies, treatment guidelines are not uniform. In a major review by Ayad et al 3 including the 14 studies, there was a significant heterogeneity as far as treatment policies were concerned. The majority of the studies favored surgery 1,14 ; whereas few others have tried radiation therapy as primary treatment. 4,15 Multimodality treatment (surgery with adjuvant radiotherapy) was also tried in some retromolar trigone series. 2,7 9,13,14 However, the patient and tumor characteristics and the treatment modalities used in these studies were not uniform and the reported outcomes were not comparable. The cause-specific survival was not mentioned in 5 of these studies. 1,6,7,16,17 Whereas in other studies, the cause-specific survival was not comparable as analysis was done using the T classification in a few studies and stage grouping in others. 2,7 9,13 The major difference between the current study and the previous 6 studies 2,7 9,13,14 is heterogeneity in patient population and treatment protocols. The current study included only patients with stage III and IVa cancer and all the patients received standard surgery followed by radiotherapy. As far as extent of surgery is concerned, there is no consensus. Some groups have advocated limited mandibular resection including marginal 18 and segmental mandibulectomy, 9,13 whereas others have advocated radical resections like hemimandibulectomy. 7,14 Kowalski et al 7 reviewed their experience on hemimandibulectomy with infratemporal fossa clearance to 114 patients with retromolar trigone tumors and documented a local control of 72.8%. Thereby, the author concluded that a more extensive resection is appropriate in patients with retromolar trigone tumors to achieve an oncological cure. Contrary to Kowalski et al, 7 Hao et al 13 emphasized on conservative bone resections. Marginal mandibulectomy was performed in those patients in whom, clinically, the tumor was abutting the mandible, whereas segmental mandibulectomy was done in cases whose mandible was involved radiologically. The local control was achieved in 82% of the patients. 13 In view of the complex anatomy, high propensity for mandibular invasion, and difficulty in treating infratemporal fossa relapse, we strongly believe that a routine hemimandibulectomy should be performed in all locally advanced retromolar trigone tumors. Hemimandibulectomy also facilitates a good infratemporal fossa clearance in these patients. In view of these factors, oncologic issues take precedence over cosmetic issues in locally advanced retromolar trigone tumors. Presence of regional metastasis to the neck nodes is a bad prognostic factor not only in retromolar trigone tumors but also in the majority of head and neck squamous cell carcinomas. Different series have reported pathological lymph nodal involvement ranging between 26% and 80% in patients with retromolar trigone tumors. 1,3,6,13 A comprehensive neck dissection was performed in all the patients in the current series because of the advanced nature of primary or clinically positive neck status. However, pathological nodal metastasis was seen in only 50% of the patients mostly involving level I and II. As far as survival was concerned, nodal involvement has emerged as an adverse prognostic factor. Results of our study indicate that by adopting an aggressive and uniform treatment policy, good outcomes can be achieved in locally advanced retromolar trigone tumors, which are otherwise difficult to treat. CONCLUSION Retromolar trigone tumors constitute a small minority of all oral cancers and the available literature is limited, mostly retrospective, and heterogeneous. The current study is one of the few series including only locally advanced retromolar trigone tumors treated with a uniform treatment policy of aggressive surgery followed by radiotherapy with good outcomes. REFERENCES 1. Byers RM, Anderson B, Schwarz EA, Fields RS, Meoz R. Treatment of squamous carcinoma of the retromolar trigone. Am J Clin Oncol 1984;7: Huang CJ, Chao KS, Tsai J, et al. Cancer of retromolar trigone: long-term radiation therapy outcome. Head Neck 2001;23: Ayad T, Guertin L, Soulières D, Belair M, Temam S, Nguyen Tân PF. Controversies in the management of retromolar trigone carcinoma. Head Neck 2009;31: Lo K, Fletcher GH, Byers RM, Fields RS, Peters LJ, Oswald MJ. Results of irradiation in the squamous cell carcinomas of the anterior faucial pillar retromolar trigone. 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