Postoperative Irradiation for Tonsillar Carcinoma

Postoperative Irradiation for Tonsillar Carcinoma

WILLIAM M. THOMPSON, M.D.,* ROBERT L. FOOTE, M.D., KERRY D. OLSEN, M.D., DANIEL J. SCHAID, PH.D., GORDON L. GRADO, M.D., STEVEN J. BUSKIRK, M.D., AND JOHN D. EARLE, M.D.

From January 1975 through July 1987 at the Mayo Clinic, 16 patients received postoperative adjuvant radiation therapy for squamous cell carcinoma of the tonsil (pathologic stage I in 4 patients, stage III in 3, and stage IV in 9). Follow-up was continued for a minimum of 2 years or until death. At 5 years, overall survival was 74% and disease-free survival was 68% for the entire group of patients. The localregional control rate at 5 years was 83% for 12 patients with pathologic stage III or IV disease; the 5year disease-free survival rate was 74%. The results with use of postoperative irradiation for stage III or IV tonsillar cancer seem superior to those for a similar historical group of patients who underwent surgical treatment only. Because the number of patients was small and the analysis was retrospective, our study may have included some undetected bias.

In 1974, Whicker and associates' described the Mayo Clinic experience with only surgical treatment for tonsillar carcinoma. They reported a rate of recurrence of carcinoma above the clavicles of 27% and a 5-year survival rate of 48% (53% of the patients had pathologic stage I or II disease). In 1979, Barrs and colleagues? updated the report by Whicker and coworkers; they found a 15 to 19% rate of recurrence of carcinoma above the clavicles and a 68% 3-year survival among patients with pathologic stage I or II disease. Patients with pathologic stage III or IV disease had a 50% rate of recurrence of carcinoma above the clavicles. The overall 5year survival rate was 42%. To improve on these results, physicians at their discretion added postoperative radiation therapy for selected patients who were thought to be at high risk for recurrence. This group of patients is the subject of our current review. From the Division of Radiation Oncology (W.M.T., R.L.F., J.D.E.), Department of Otorhinolaryngology (K.D.O.), and Cancer Center Statistics (DJ.S.), Mayo Clinic Rochester, Rochester, Minnesota; Division of Radiation Oncology (G.L.G.), Mayo Clinic Scottsdale, Scottsdale, Arizona; and Department of Radiation Oncology (SJ.B.), Mayo Clinic Jacksonville. Jacksonville, Florida. *Current address: Augusta, Georgia. Address reprint requests to Dr. R. L. Foote, Division of Radiation Oncology, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905. Mayo Clin Proc 1993; 68:665-669

The role of postoperative adjuvant radiation therapy in tonsillar carcinoma has not been well defined. In a recent retrospective review from Memorial Sloan-Kettering Cancer Center,' patients with stage III or IV disease had improved local control with combined-modality treatment (that is, surgical resection in combination with either preoperative or postoperative radiation therapy). Because of a higher incidence of distant metastatic lesions, however, survival was not significantly improved over that of patients treated surgically or with radiation therapy only. Ofthe 51 patients who were given combined-modality therapy, 25 received postoperative irradiation. This group of patients was not analyzed separately from the 26 patients who received preoperative radiation therapy. Herein we describe our experience with postoperative radiation therapy for tonsillar carcinoma.

MATERIAL AND METHODS From January 1975 through July 1987, 16 patients underwent both complete surgical resection and postoperative adjuvant radiation therapy at the Mayo Clinic for squamous cell carcinoma of the tonsil. Additional patients with tonsillar carcinoma underwent surgical resection at the Mayo Clinic but for various reasons received postoperative radiation therapy at another institution. Our study is limited to the patients who received all their treatment at the Mayo Clinic. Data from these patients were collected and analyzed in July 665

© 1993 Mayo Foundation for Medical Education and Research

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1989. The median age of the 12 men and 4 women was 61 years (range, 53 to 74). At the time of surgical resection, all patients were free of distant disease as determined on the basis of a complete medical history and the results of physical examination, chest roentgenography, complete blood cell counts, and blood chemistry studies. Surgical approaches were transoral resection in seven patients, mandibular osteotomy in six, composite resection in two, and pharyngotomy in one. All margins of resection examined were free of tumor. Of the 16 study patients, 13 underwent unilateral neck dissection. A median of 25 lymph nodes (range, 15 to 37) was examined in each specimen from neck dissection. Three patients did not undergo neck dissection. Of the 13 specimens from neck dissection, 12 contained nodal metastatic lesions, and 4 of them had microscopic or gross extracapsular nodal extension. The metastatic nodes ranged from 1.5 to 6.0 ern. From one to six (median, three) lymph nodes were involved. Histologically, the tonsillar carcinoma was grade 1 in one patient, grade 2 in four, grade 3 in eight, and grade 4 in three. The soft palate was involved in eight patients, the base of the tongue in five, and the pharyngeal wall in one. No patient had involvement of the nasopharynx or larynx. The tonsillar carcinomas were pathologically staged retrospectively in accordance with the 1988 criteria from the American Joint Committee on Cancer (Table 1). Four patients had stage I cancer, three had stage III, and nine had stage IV. The main indications for postoperative adjuvant radiation therapy were advanced neck disease in nine patients and transoral resection of an enlarged tonsil that unexpectedly contained carcinoma in three patients. The four other patients were treated for various reasons, including high-grade tumors, close margins, nodal metastatic involvement, or a combination of these factors. Radiation therapy was initiated, on the average, 35 days postoperatively (range, 5 to 63; median, 33) and was continued for a median of 58 days (range, 45 to 68). The total dose to the primary tumor bed was 40 to 66 Gy (median, 55.8). The fraction size was 1.8 Gy in 11 patients, 1.96 Gy in 1, and 2.0 Gy in 4. The median number of fractions delivered was 31 (range, 20 to 36). Nine patients received 55.8 Gy or more to the primary site. Irradiation to the neck was administered bilaterally in 13 patients. Of the three patients who did not receive bilateral neck irradiation, one received irradiation to the primary site only and two received irradiation to the primary site and the ipsilateral neck only. For the irradiation to the neck, the dose ranged from 40 to 66.6 Gy (median, 50.4). Eight patients were treated with cobalt-on and eight with 6-MV photons. For all patients, follow-up continued for a minimum of 2 years (nine patients) or until death (seven patients). Two

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Table I.-Pathologic Stage of Tonsillar Carcinoma in 16 Patients According to the 1988 Criteria From the American Joint Committee on Cancer Nodal involvement

Primary tumor

NO

Nl

N2a

N2b

Total

T1 T2 T4 Total

4* 0 0 4

2 I 0 3

I 0

2 5 1 8

9 6 I 16

0 1

*Three patients with clinical stage NO(no metastatic involvement of regional lymph nodes) did not undergo neck dissection.

years was chosen as the minimal follow-up period because all local recurrences, neck recurrences, distant metastatic growths, and deaths due to tonsillar cancer had occurred within 20 months, except for one patient in whom a delayed metastatic lesion developed in the untreated opposite side of the neck at 3 years and who underwent surgical salvage. No patients were lost to follow-up. The duration of follow-up for survivors was from 3.5 to 12.6 years (median, 8.6). Demographic, treatment, and pathologic variables were analyzed to discover factors associated with improved control of disease above the clavicles, disease-free survival, and overall survival. The three groups of variables analyzed were (1) gender and age at operation; (2) interval between operation and radiation therapy, total radiation dose, dose per fraction, overall duration of radiation therapy, presence or absence of irradiation administered to the neck, and extent of surgical resection; and (3) number of nodes examined in the specimen from neck dissection, grade of tumor, involvement of soft palate or base of tongue, clinical and pathologic stage of tumor, pathologic stage of disease in the neck, presence or absence of extracapsular nodal extension, and overall pathologic stage. The prognostic value of variables was assessed by comparing the survival distributions or the time until recurrence of disease of a specific variable with the log-rank statistic.' The survival distributions were estimated by using the Kaplan-Meier method.' These curves were calculated in two ways-by considering deaths due to intercurrent disease as failures for disease-free survival and then as deaths for overall survival and by considering deaths due to intercurrent disease as censored. We thought that the latter method was more appropriate for cause-specific deaths. Because the two methods were generally consistent, we considered deaths due to intercurrent disease as censored. Multivariate statistical analysis was not performed because the patient population was small and no findings were significant on univariate analyses. Local control rates were compared by using Fisher's exact test for the comparison of proportions.

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RESULTS 100 At 5 years, the overall survival was 74% and the disease-free survival was 68% for the entire group of 16 study patients Overall 80 (Fig. 1). As of July 1989, nine patients (56%) were alive without evidence of disease, three (19%) had died of Disease-free 60 intercurrent disease, and four (25%) had died of tonsillar % carcinoma. 40 In four patients, the first recurrence was local, appearing 20 within 11 months after completion of radiation therapy. These four patients died within 13 months after the recurrent oL-_---JL..-_---'_ _- - '_ _--'-_ _--l..._ _-..J lesions were detected. One patient died of local recurrence 4 o 2 6 8 10 12 Years only, two died of local recurrence and distant metastatic involvement, and one died of local recurrence, metastatic disease in the contralateral neck, and distant metastatic tumor. Only one patient had recurrence in an untreated neck. Fig. 1. Overall and disease-free survival for entire group of 16 study patients who received postoperative adjuvant radiation In this patient, who had involvement of the soft palate, therapy for tonsillar carcinoma. metastatic disease developed in the contralateral neck (as the only site of recurrence) 3 years after radiation therapy to the tumor bed and ipsilateral neck; this event was included in the Osteoradionecrosis of the right posterior maxilla and right disease-free survival (Fig. 1). The patient was free of disease mandible developed in one patient. The teeth of this patient 6 years after a neck dissection. No patient had recurrence in were removed, and the wounds were allowed to heal by seca treated neck as the only site of recurrence. Eleven patients ond intention. No further surgical intervention was needed. have remained continuously free of disease. Data on local control, 5-year disease-free survival, and 5- DISCUSSION year overall survival for various treatment and pathologic No significant prognostic factors were discovered in our variables are summarized in Table 2. Because of the small analyses of demographic, treatment, and pathologic varinumber of patients, none of the differences was significant. ables in 16 patients who received postoperative radiation A trend was suggested toward improved local control, 5-year therapy for tonsillar carcinoma. Because of the small numdisease-free survival, and 5-year overall survival with low- ber of patients in our study, the trend toward improved grade tumors, with total radiation dose of more than 55.8 Gy, outcome with use of a radiation dose that exceeded 55.8 Gy or with no involvement of the tongue and soft palate. No and lack of involvement of the soft palate or the base of the relationship was noted between age (61 years or younger tongue should be interpreted with caution. Moreover, other versus older than 61 years), gender, stage of disease in the features that were evaluated may have prognostic imporneck, extracapsular nodal extension, number of nodal meta- tance but may not have been revealed because of the small static lesions, or fraction size and local control, disease-free number of patients. survival, and overall survival. Of note, no recurrences were Twelve patients with pathologic stage III or IV disease detected within an irradiated field in the neck despite the underwent a composite resection, mandibular osteotomy, or pathologic presence of metastatic disease in 12 necks. More pharyngotomy, with or without a neck dissection, and postthan two lymph nodes were involved in 6 of the 12 necks, operative radiation therapy. In these 1:4 patients, the rate of and the pathologic stage of the cancer was N2 in 9. Further- disease-free survival was 74%, the rate of overall causemore, extracapsular nodal extension was noted in four of the specific survival was 83% (75% survival for death from all necks. causes), and the local-regional control rate at 5 years was The three local recurrences in patients with pathologic Tl 83%. Although the patient population was small, the results or T2 tumors were of concern. Review of the simulation and suggest an improvement in control of cancer above the port films confirmed a marginal recurrence along the inferior clavicles and survival in comparison with results in historical edge of the radiation beam in one patient after administration control patients at the Mayo Clinic who received surgical of 55.8 Gy. The two other patients received a relatively low treatment only. In the most recent report about those padose of irradiation: 54 Gy in 64 days and 49 Gy in 59 days, tients, the 5-year survival for death from all causes was 42%, both with a planned 3-week midtreatment break and only and the local-regional control rate was 50%.2 That patient population, with a mean age of 60 years and a male-toone field of an opposed lateral pair treated each day. We observed no soft tissue necrosis or trismus in our female ratio of 2.3: 1, was similar to the patient population in group of patients. All patients experienced xerostomia. the current study.

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Table 2.-Local Control, 5-Year Disease-Free Survival, and 5-Year Overall Survival for Patients With Tonsillar Carcinoma Who Received Postoperative Irradiation

Variable

No. of patients

Local control

5-yr survival (%) Free of disease Overall

No.

%

7

5

I

I

6 2

5 1

71 100 83 50

70 100 67

70 100 83

9 6 1

7 5 0

78 83

65 83

75 83

5 11

3 9

60 82

60 72

60 80

8 8

5 7

62 88

47 88

60 88

5

5 7

100 64

75

100

11

64

64

Total radiation dose (Gy) ::;55.8 >55.8

9 7

6 6

67 86

56 86

67 86

Interval from operation to irradiation (days) ::;30 >30

7 9

5 7

71 78

71 65

71 76

Duration of radiation therapy (days) ::;58 >58

9 7

6 6

67 86

65 71

65 86

Overall pathologic stage of disease I III IV

4 3 9

2 3 7

50 100 78

50 67 78

50 100 78

16

12

75

68

74

Surgical procedure Transoral resection Pharyngotomy Osteotomy Composite Stage of primary tumor Tl

T2 T4 Tongue involved Yes No Soft palate involved Yes No Grade of tumor lor 2 30r4

Overall study group

CONCLUSION The survival results and local-regional control rates we report for patients with stage III or IV tonsillar cancer who were given postoperative radiation therapy are excellent in comparison with other retrospective reviews of similar patients who underwent surgical resection only, radiation therapy only, or preoperative radiation therapy and surgical resection (Table 3). On the basis of our limited experience, we recommend that postoperative radiation therapy be considered for completely resected stage III or IV squamous cell carcinoma of the tonsillar fossa. This recommendation is

further supported by the recently updated experience of Perez and associates," who reported improved control in selected cases of T3 or T4 tumors with use of a combination of surgical treatment and postoperative radiation therapy. REFERENCES 1. Whicker JH, DeSanto LW, Devine KD. Surgical treatment of squamous cell carcinoma of the tonsil. Laryngoscope 1974; 84:90-97 2. Barrs DM, DeSanto LW, O'Fallon WM. Squamous cell carcinoma of the tonsil and tongue-base region. Arch Oto1aryngol 1979; 105:479-485

TONSILLAR CARCINOMA

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Table 3.-Summary of Published Studies of Survival and Control Rates With Use of Various Treatment Modalities in Patients With Tonsillar Carcinoma Treatment modality*

Study Perez et al"

Whicker et al' Barrs et aJ2 Quenelle et al?

RT RT+S RT RT+S S S RT+S

Givens et al"

S RT RT+S

Fayos & Morales?

RT

Mendenhall et al'"

RT

Spiro & Spiro"

Wong et al" Perez et al" Current series

S,RT,RT+S, S+RT SorRT RT+S orS +RT RT RT RT+S S+RT S+RT S+RT

No. of patients

Cancer stage

5-yr survival (%)

11 16 19 14 86 48 40 4 2 4 11 23 9 18 118

45.4 11.1 15 25 48 42 62.5 (2 yr) 25 (2 yr)

29 51 78

III III IV IV I-IV III, IV III IV III IV III IV III IV III IV III IV III, IV

34 44 62 64 127 133 36 3 9

III, IV III, IV III IV I-IV I-IV I-IV III IV

III

75 37.5 4 0 20 49 33 64

24 42

Control above clavicle (%)

73 50 100 75 45 74 89 67 79 55 76 98

75 60

100 78

31 38 58 100 78

*RT =radiation therapy, with or without neck dissection; RT + S = planned preoperative irradiation; S =surgical treatment only; S + RT =planned postoperative irradiation.

3.

Spiro JD, Spiro RH. Carcinoma of the tonsillar fossa: an update. Arch Otolaryngol Head Neck Surg 1989; 115:1186-

4.

Mantel N. Evaluation of survival data and two new rank order statistics arising in its consideration. Cancer Chemother Rep 1966; 50:163-170 Kaplan EL, Meier P. Nonparametric estimation from incomplete observations. J Am Stat Assoc 1958; 53:457-481 Perez CA, Mill WB, Ogura JH, Powers WE. Carcinoma of the tonsil: sequential comparison of four treatment modalities. Radiology 1970; 95:649-659 Quenelle DJ, Crissman JD, Shumrick DA. Tonsil carcinoma-treatment results. Laryngoscope 1979; 89:1842-1846 Givens CD Jr, Johns ME, Cantrell RW. Carcinoma of the tonsil: analysis of 162 cases. Arch Otolaryngol 1981; 107:730-734

1189

5. 6. 7. 8.

9.

Fayos JV, Morales P. Radiation therapy of carcinoma of the tonsillar region. Int J Radiat Oncol Bioi Phys 1983; 9: 139144 10. Mendenhall WM, Parsons IT, Cassisi NJ, Million RR. Squamous cell carcinoma of the tonsillar area treated with radical irradiation. Radiother Oncol 1987; 10:23-30 II. Wong CS, Ang KK, Fletcher GH, Thames HD, Peters LJ, Byers RM, et al. Definitive radiotherapy for squamous cell carcinoma of the tonsillar fossa. Int J Radiat Oncol Bioi Phys 1989; 16:657-662 12. Perez CA, Carmichael T, Defineni VR, Simpson JR, Fredrickson J, Sessions D, et al. Carcinoma of the tonsillar fossa: a nonrandornized comparison of irradiation alone or combined with surgery; long-term results. Head Neck 1991; 13:282-290