Surgical management of squamous cell carcinoma of the base of the tongue

Surgical Management of Squamous Cell Carcinoma of the Base of the Tongue Dennis H. Kraus, MD, A. Paul Vastola, MD, Andrew G. Huvos, MD, Ronald H. Spiro, MD, NewYork, NewYork

An I 1-year experience with 100 patients who had surgery as definitive treatment for squamous cell carcinoma of the base of the tongue between 1979 and 1989 has been retrospectively reviewed. Although 81% of the patients had stage III or stage IV disease, mandible continuity was maintained in 86%, and the larynx was preserved in 80%. Lymphadenectomy was performed in conjunction with the primary resection in a total of 8 9 patients, including 6 2 patients who had clinically evident metastases. Postoperative radiation was administered to 63 patients because of positive resection margins ( 1 7 ) , positive cervical lymph nodes ( 3 4 ) , or high tumor stage ( 1 2 ) . Overall and disease-specific 5-year survival rates for the entire group were 55% and 65%, respectively. The 5-year diseasespecific survival rates for stages I/II, III, and IV were 77%, 64%, and 59%, respectively. Local control was achieved in all but 18 patients. Our results indicate that surgery remains a viable treatment option for patients with advanced base-of-tongue cancer. Prospective trials are necessary to compare surgery versus definitive radiotherapy with respect to patients' survival and quality of life.

Fromthe Headand NeckService(DHK,APV,RHS), Departmentof Surgery,and the Departmentof Pathology(AGH), MemorialSloanKetteringCancerCenter,New York,New York. Requestsfor reprintsshouldbe addressedto DennisH. Kraus,MD, MemorialSloan-KetteringCancer Center, Box 285, 1275 York Avenue, New York,New York 10021. Presentedat the 39th AnnualMeetingof the Societyof Head and Neck Surgeons,Los Angeles,California,March 18-21, 1993. 384

with squamous cell carcinoma of the base of the p ~atients tongue commonly present with advanced-stage disease, which is either due to extensive local invasion or to the carcinoma spreading to the cervical lymph nodes. Currently, treatment options include surgery (with or without postoperative radiation therapy), external-beam radiation therapy (including hyperfractionation), external-beam radiation therapy with brachytherapy implantation (with or without neck dissection), and induction chemotherapy with external-beam radiation therapy (with or without brachytherapy implantation). Morality selection usually depends on the training and experience of the oncologist who is treating the tongue cancer. Comparisons between modalities are difficult because of inherent selection bias, and there is minimal information about the impact of treatment on patients' speech and swallowing. More than 25 years have elapsed since the last report from our hospital that specifically focused on the surgical management of base-of-tongue cancer. This study was undertaken in order to document some of the dramatic changes that have occurred with respect to the contemporary surgical management of squamous cell carcinoma of the base of the tongue. PATIENTS AND METHODS We retrospectively reviewed the charts of 323 patients who consecutively obtained treatment for squamous cell carcinoma of the base of the tongue at Memorial SloanKettering Cancer Center from 1979 to 1989. A total of 223 patients were excluded from the current study due to a pathology other than squamous cell carcinoma, previous treatment, treatment with chemotherapy or radiation therapy only, error in site designation, or inadequate or incomplete information. This study is based on the remaining 100 patients with base-of-tongue squamous cell carcinoma, whose primary tumors were resected. There were 64 men and 36 women. The median age was 59 years (range: 29 to 83 years). Tumors were staged according to the TNM clinical staging system proposed by the American Joint Committee on Cancer [1]. Twelve, 43, 26, and 19 patients had stage T1 to T4 disease, respectively, and 38, 36, 22, and 4 patients had NO to N3 disease, respectively. Only 20% of patients had localized disease. The remaining 80% had clinical stage III or stage IV disease, including 18 patients who had a clinically negative neck. Overall, 62% of patients presented with a clinically involved neck. The distribution of patients by clinical stage is represented in Table I. Resection of the primary site was performed via mandibulotomy in 59 patients, composite resection in 15 patients, transcervical approach in 13 patients, transhyoid approach in 8 patients, and peroral approach in 5 patients. Involvement of the supraglottic larynx necessitated

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supraglottic !aryngectomy in 16 patients. A total of 20 patients underwent laryngectomy for either direct invasion of the larynx or due to a significant risk of aspiration. The mandible remained in continuity in 86% of patients (Table II). Primary surgical repair was performed in 84 patients, and a pectoralis major myocutaneous flap was employed in 16. Management of the cervical lymphatics (Table III) included comprehensive neck dissection in 71 patients, supraomohyoid neck dissection in 8, bilateral radical neck dissection in 5, bilateral supraomohyoid neck dissection in 4, radical neck dissection and supraomohyoid neck dissection in 1, and observation in 11. Procedures in 38 patients whose necks were staged NO included radical neck dissection in 17, observation in 11, supraomohyoid neck dissection in 7, and bilateral supraomohyoid neck dissection in 3. Management of the 62 patients with N + neck included unilateral radical neck dissection in 50, extended radical neck dissection in 4, bilateral radical neck dissection in 5, ipsilateral radical neck dissection with a contralateral supraomohyoid neck dissection in 1, supraomohyoid neck dissection in 1, and bilateral supraomohyoid neck dissection in 1. Postoperative radiotherapy was given as an adjunct to surgery in 63 patients. This included 17 patients with positive resection margins, 15 of whom also had cervical lymph node metastases. Of the remaining 46 patients with negative surgical margins, lymph node metastases were present in 34. The median postoperative radiation dose for all irradiated patients was 6,000 cGy (range: 4,800 to 7,000 cGy). Radiotherapy was administered in our hospital in only 11 patients (17%), each of whom received doses of 6,000 to 6,500 cGy. The remaining patients received their radiation elsewhere. Radiotherapy data were obtained by reviewing hospital charts and treatment summaries. Follow-up was complete as of January 1, 1993. The median follow-up was 3.3 years (range: 0.2 to 11.3 years). The site of recurrence, disease status at last follow-up, and salvage therapy (when appropriate) were recorded. All patients not seen prior to the conclusion of the study were contacted by telephone. The date and location of first occurrence following definitive treatment at our institution were used to determine treatment failure rates. Overall survival was graphically depicted according to the method of Kaplan and Meier [2]. The log-rank test was used to compare results between subgroups [3]. RESULTS On final pathology, surgical resection margins were positive in 21 patients. Of 89 patients who had a lymphadenectomy, metastases were present in 68. Nodes proved positive in 13 of 27 patients who had an dective node dissection, whereas the specimen proved negative in 7 of 62 patients considered N + clinically. Measurement of tumor thickness was possible, retrospectively, in all but two patients, using the same techniques we have reported in patients with oral cavity cancer [4]. The tumor was less than 4 mm in 11 patients, 4 to 8 mm in 39, and greater than 8 mm in 48.

TABLE I Clinical Stage of Disease

NO N1 N2 N3 Total

T1

T2

T3

T4

6 3 1 2

14 22 6 1

11 8 7 0

7 3 8 1

38 36 22 4

12

43

26

19

1O0

T1-T4 = levelsof tumor involvement;NO-N3 = levelsof nodal involvement.

TABLE II Treatment of the Primary Cancer Mandibulotomy Resection BOT Supraglottic Laryngectomy

59 43 11 5

Composite resection Segmental Segmental/laryngectomy Marginal

15 12 2 1

Cervical approach Laryngectomy Supraglottic Resection BOT

21 13 5 3

Per oral resection BOT

5

BOT = baseof tongue.

TABLE Ill Treatment of the Neck Total No: of

Procedures

Procedures

NO

N+

Comprehensive neck dissection Supraomohyoid neck dissection Bilateral supraomohyoid neck dissection Bilateralcomprehensive neck dissection

17

54

71

7

1

8

3

1

4

0

5

5

Comprehensive neck dissec-

0

1

1

tion/supraomohyoid neck dissection No nodal dissection

11

0

11

N+ = N1-N3.

Complications occurred in 41 patients (Table IV); there were no postoperative deaths. Wound problems and pulmonary compromise were the most:common complications. Wound infections occurred in 12 patients, and fistulas were recorded in 10 patients, 2 of whom also had partial flap necrosis. No secondary repairs were required.

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TABLE IV

Complications Local wound sepsis Fistula Transient febrile illness Aspiration pneumonia Seroma Partial flap necrosis Flap edema Urinary retention Congestive heart failure Osteoradionecrosis Seizure

12 10 7 6 3 2 1 1 1 1 1

TABLE V

Factors Influencing Survival Factors

2-Year

5-Year

Overall survival

69

55

Cause-specific survival T1 and T2 T3 and T4 NO N1, N2, and N3 Stage I and II Stage III and IV Negative resection margins Positive resection margins Pathologically negative neck Pathologically positive neck Larynx preservation Laryngectomy Surgery Combination therapy Thickness <0.4 cm Thickness 0.4-0.8 cm Thickness > 0.8 cm

74 79 68 85 67 89 70 75 67 93 65 79 51 74 74 70 78 70

65 66 65 79 57 77 62 68 52 782 58 71 39 71 61 60 72 58

p Value

0.55 0.21 0.55 0.68 0.14 0.0004 0.98 0.84*

T1-T4 = levels of tumor involvement; N0-N3 = levels of nodal involvement. *Survival-comparedthickness: < 0.7 and > 0.6.

TABLE VI Site of Recurrence Site

Number of Instances

Local Local/regional Local/regional/distant Local/distant Regional Regional/distant Distant

7 5 2 4 8 2 14

Total

42

Cumulative and cause-specific survival rates at 5 years were 55% and 65%, respectively. At the conclusion of the study, 48 patients were alive and well, 6 were living with disease, 34 had died of disease, and 12 had died of other causes. Cause-specific survival is listed in Table V. 386

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Survival was not significantly influenced by T stage, tumor thickness, nodal involvement, or the status of the surgical margins. When larynx preservation was possible, survival was better when compared with those who required laryngectomy. No survival difference was apparent when patients who had only surgery were compared with those who had combined therapy. Treatment failure in 42 patients involved the primary site in 18, the neck in 17, and distant sites in 22 (Table VI). A total of 28 patients had a locoregional recurrence with or without distant metastases. Only two patients with locoregional recurrence achieved salvage with additional therapy. Local recurrence occurred in 18 patients, including 4 of 21 (19%) who had positive margins and 14 of 79 (18%) who had negative margins. Postoperative radiotherapy was given to 17 of the 21 patients with positive margins, including the 4 who experienced local recurrence. Of the 79 patients with negative margins, 46 received postoperative radiotherapy, including 9 of the 14 (20% of those irradiated) who developed a local recurrence. Only 5 (15%) of the 33 patients with negative margins who did not receive postoperative radiotherapy had failure at the primary site. Of 68 patients with confirmed neck metastases, 49 received postoperative radiotherapy and 19 did not. Neck failure was noted in 18% (9 of 49) who received postoperative radiotherapy and in 21% (4 of 19) of those who were not irradiated. In 32 patients whose lymph nodes were uninvolved, cancer of the neck recurred in 12.5% (4 of 32), with a similar incidence of recurrence regardless of whether radiation was postoperatively utilized. Distant metastases were documented in 22 patients, 14 of whom had no other evidence of treatment failure. As a function of clinical stage, no patients with stage I, 7% with stage II, 11% with stage III, and 22% with stage IV developed distant metastases. Cervical lymph node metastasis was noted in 86% (12 of 14) of these patients. COMMENTS Within the past 50 years, there have been 4 reports from the Memorial Hospital's Head and Neck Service, concerned with almost 3,000 tongue cancer patients [5-8], but it has been 25 years since we have focused specifically on squamous carcinomas arising in the base of the tongue [7]. Although the tumors in the present study were evidently much less extensive than those described in the latter study, the stage distribution was similar to that which we last reported for base of tongue cancers [8]. Then, as now, fewer than 20% of patients present with tumors that are confined to the primary site (NO). One ongoing trend, however, has been the increasing proportion of women with tongue cancer, which was 34% in this study. This almost certainly relates to increasing cigarette consumption by women in recent decades. The surgical management of base-of-tongue cancer has changed significantly in recent years. In our last review, 31% of tongue-base resections involved a composite procedure, and 42% required a laryngectomy. Only 14% and 20% of our current patients had a jaw resection

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or a laryngectomy, respectively. Our preference for the median or paramedian mandibulotomy approach to cancers arising in the base of tongue has been reported elsewhere [9]. Although it has provided excellent exposure for resection in properly selected patients, margins were positive for tumors in 21% of our patients. A 25% incidence of resection margin involvement has also been noted by Dupont et al [10]. Delineation of tumor extent in the base of the tongue can be a problem, particularly when the tumor has ill-defined borders. Our current survival rates show a significant improvement over those previously reported, undoubtedly due to better locoregional tumor control. The efficacy of any treatment modality can rarely be established by a retrospective analysis, but we are certain that our improved disease control in the primary site and the neck is directly related to more aggressive use of postoperative radiation therapy. The role of postoperative radiotherapy as an adjunct to resection of base-of-tongue cancer and cancer at other sites has been well-established by Zelefsky [11] and Vikram [12-15]. Nearly all of our patients with stage III- and stage IV-confirmed nodal metastasis currently receive combination therapy, usually to a full therapeutic dose, A similar strategy is employed in patients whose surgical specimens show positive margins or unusually aggressive histologic features. The fact that we are retrospectively unable to confirm that combination therapy significantly improved survival when compared with surgery alone relates to inherent treatment selection bias: patients with more advanced disease more often received radiation in addition to surgery. This study suggests a striking increase in distant metastasis (22 of 100 patients; 52% of those with confirmed recurrence) compared with the 29% incidence of distant spread recorded by Callery et al [8] in those who died with uncontrolled base-of-tongue cancer. Some of this increase can be anticipated as a consequence of improved locoregional control and longer survival. It seems unlikely that results will continue to improve, unless more effective adjuvant chemotherapy becomes available for this high-risk patient population. Aggressive management of the cervical lymphatics also appears to have played a role in our patients' improved survival. All patients whose metastases were clinically apparent had neck dissections, almost always comprehensive, which were bilateral when indicated. Only 29% of those whose necks were clinically negative were observed. The remainder either had a comprehensive or staging neck dissection. Although there was a trend towards improved survival when the neck was clinically and pathologically negative, the difference was not statistically significant. Similar results were noted in our previous report and by Thawley and coworkers [16], although Weber et al [17] has been able to confirm a statistically significant impact of nodal involvement. Our inability to significantly correlate survival with T stage, tumor thickness, resection margin status, or nodal involvement came as somewhat of a surprise. In all probability, much of this discrepancy is a direct reflection of the

inadequacy of current clinical staging criteria as they apply to squamous cancers arising in the base of the tongue. The need for concomitant laryngectomy evidently selected out those who had the most extensive tumors, irrespective of T stage, which probably explains why this was the only significant predictor of decreased survival. Clearly, several options exist for the management of patients with squamous carcinoma in the base of the tongue. Radiotherapy is preferred in many centers. Conventional external-beam radiotherapy has been utilized in patients with exophytic tumors and has resulted in excellent local control and overall survival [17]. A combination of external-beam radiotherapy with a brachytherapy boost has been advocated by Harrison et al [18] at Memorial Hospital; they report excellent local control and actuarial survival. Similar results have been reported from other institutions [19-21]. Whatever radiation modality is employed, results in patients with large deeply invasive tumors have been poor. Parsons and coworkers [22] has reported local control rates of only 22% in patients with T4 primary tumors treated with external beam radiotherapy. Foote et al [23] noted improved local control in patients with twice-daily radiation fractions and concluded that interstitial implantation is not essential for successful radiotherapeutic treatment of base-of-tongue carcinoma. Wang [24] and Pinto et al [25] have also described improved survival and limited morbidity when patients with advanced oropharyngeal cancer were treated with hyperfractionation techniques. Our experience indicates that good local control and survival can be achieved with the use of surgery in appropriately selected patients. Larger, well-defined tumors can usually be resected with mandible and larynx preservation. Elaborate reconstruction has usually not been necessary, and results, in terms of speech and swallowing, have usually been quite satisfactory. Objective measurement of these functions was not available in this retrospective study. Prospective trials are necessary in order to compare functional results in patients treated definitively with surgery or radiation therapy. Results remain disappointing in patients with the most advanced tumors that require a laryngectomy. Our current practice is to offer these patients larynx preservation through the aggressive use of chemotherapy and radiation, reserving surgery for salvage [26,27]. REFERENCES 1. American Joint Committeeon Cancer. Manual for staging of cancer. 3rd ed. Philadelphia: JB Lippincott, 1987. 2. Kaplan EL, Meier P. Nonparametric estimation from incomplete observations.Journal of the AmericanStatisticalAssociation 1958; 53: 457-61. 3. Peto R, Pike MC. Design and analysisof randomizedclinical trials requiring prolongedobservationsof each patient. II. Analysis and examples. Lancet 1977; 35: 1-39. 4. Spiro RH, Huvos AG, Wong GY, et al. Predictive value of tumor thickness in squamous carcinoma confined to the base of tongue and floor of mouth. Am J Surg 1986; 152: 345-50. 5. Martin ME, Munster M, SugarbakerED. Cancerof the tongue.

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Arch Surg 1940: 41: 888-936. 6. Frazell EL, Lucas JC. Cancer of the tongue. Report of the management of 1554 patients. Cancer 1962; 15: 218-32. 7. Harold CC. Surgical treatment of cancer of the base of the tongue. Am J Surg 1967; 114: 493-7. 8. Callery CD, Spiro RH, Strong EW. Changing trends in the management of squamous carcinoma of the tongue. Am J Surg 1984; 148: 449-54. 9. Dubner S, Spiro RH. Median mandibulotomy: a critical assessment. Head Neck 1991; 13: 389-93. 10. Dupont JB, Guillamondegui OM, Jesse R. Surgical treatment of advanced carcinomas of the base of the tongue. Am J Surg 1978; 136: 501-3. 11. Zelefsky M J, Harrison LB, Fass DE. Armstrong JG. Postoperative radiation therapy for advanced oropharyngeal carcinoma: long term treatment results. Cancer 1992; 70: 2388-95. 12. Vikram B, Strong EW, Shah JP, Spiro R. Failure at the primary site following multi-morality treatment in advanced head and neck cancer. Head Neck 1984; 1: 720-3. 13. Vikram B. Strong EW, Shah JP, Spiro R. Failure in the neck following multi-modality treatment for advanced head and neck cancer. Head Neck 1984: 1: 724-9. 14. Vikram B, Strong EW, Shah JP, Spiro R. Failure at distant sites following multi-modality treatment for advanced head and neck cancer. Head Neck 1984; 1: 730-3. 15. Vikram B. Strong EW, Shah JP, Spiro R. Second malignant neoplasms in patients successfully treated with multi-modality treatment for head and neck cancer. Head Neck 1984; 1: 734-8. 16. Thawley SE, Simpson JR, Marks JE, Perez CA, Ogura JH. Preoperative radiation in surgery for carcinoma of the base of the tongue. Ann Otol Rhinol Laryngol 1983: 92: 485-90. 17. Weber RS. Gidley P. Morrison WH, et al. Treatment selection for carcinoma of the base of the tongue. Am J Surg 1990: 160: 415-9. 18. Harrison LB, Zelefsky M J, Sessions RB, et al. Base-of-tongue cancer treated with external beam radiation plus brachytherapy:

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oncologic and functional outcome. Radiology 1992: 184: 267-70. 19. Goffinet D, Fee W, Wells J, et al. 192-iridium pharyngoepiglottic fold interstitial implants: the key to successful treatment of base of tongue carcinoma by radiation therapy. Cancer 1985; 55: 941-8. 20. Puthawala A, Syed A, Eads D, et al. Limited external beam and interstitial 192-iridium irradiation in the treatment of carcinoma of the base of the tongue: a ten year experience. Int J Radiat Oncol Biol Plays 1987; 14: 839-48. 21. Housset M. Baillet F, Dessard-Diana B, et al. A retrospective study of three treatment techniques for T1-T2 base of tongue lesions: surgery plus post operative radiation, external radiation plus interstitial implantation, and external radiation alone. Int J Radiat Oncol Biol Phys 1987; 13: 511-6. 2 2 . Parsons JT, Million RR, Cassisi NJ. Carcinoma of the base of the tongue: results Of radical radiation with surgery reserved for radiation failure. Laryngoscope 1982: 92: 689-96. 23. Foote RL, Parsons JT, Mendenhall WM, Million RR, Cassisi N J, Stringer SP. Is interstitial implantation essential for successful radiotherapeutic treatment of base of tongue carcinoma? Int J Radiat Oncol Biol Phys 1990: 18: 1293-8. 24. Wang CC. Local control of oropharyngeal carcinoma after two accelerated hyperfractionation radiation therapy schemes. Int J Radiat Oncol Biol Phys 1988; 14:1143-6. 25. Pinto LH, Canary PC, Araujo CM, Bacelar SC. Souhami L. Prospective randomized trial comparing hyperfractionated versus conventional radiotherapy in stages III and IV oropharyngeal carcinoma. Int J Radiat Oncol Biol Phys 1991; 21: 557-62. 26. Pfister DG, Strong EW, Harrison LB, Kraus DH. Larynx preservation treatment in head and neck cancer. In: Fortner JG, Rhoades JE, editors. Accomplishments in cancer research, 1991. Philadelphia: JB Lippincott. 1992: 240-50. 27. Pfister DG, Strong EW, Harrison LB, et al. Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer. J Clin Oncol 1991; 9: 850-9.

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