Analysis of adenoid cystic carcinoma treated by radiotherapy Yoichiro Hosokawa, DDS, PhD,a Keiichi Ohmori, DDS, PhD,b Masanori Kaneko, DDS,a Michio Yamasaki, MD, PhD,C Mohiuddin Ahmed, BDS,d Takuro Arimoto, MD,e Goro Irie, MD, PhDf Sapporo, Japan HOKKAIDO
The records of 41 patients with adenoid cystic carcinoma of the head and neck region who had been treated with radiotherapy were reviewed. Local control was achieved in 72.3% in the cases with primary lesions at 5 years. The prognosis for tumors that arose in the major salivary glands was better than that for tumors that arose in the minor salivary glands; however, the difference was not statistically significant. In the minor salivary glands, early-stage tumors were well controlled with the use of radiation therapy alone. In spite of the high local control rate, the disease-free survival rate of the patients at IO years was only 20.8%. Lung metastasis determined the prognosis. (ORAL SURC ORAL MED ORAL PATHOL 1992;74:251-5)
denoid cystic carcinoma (ACC) is a rare tumor, but clinically it should not be disregarded because ACC shows a long natural course and a high recurrence rate.’ The treatment of ACC has been controversial. A retrospective analysis of ACC is presented in this article with special attention to the control rate in relation to the modality of treatment used. Special attention is given to radiation therapy. MATERIAL AND METHODS
This study reports on 4 1 patients with adenoid cystic carcinoma of the head and neck who were treated with radiation at The Hokkaido University from March 1969 to September 1990. Twenty two of the patients were men and 19 were women; 33 were primary occurrences and 8 were local recurrences. The average age of the patient at detection of the primary lesion was 57.6 years. Clinical details for the casesare shown in Tables I through III; and treatment of primary sites in Table I, tumor location in Table II, and metastasis in Table III.
*Instructor, Department of Dental Radiology. bLecturer, Department of Dental Radiology. CProfessor,Department of Dental Radiology. dGraduate student, Department of Oral Surgery. eLecturer, Department of Radiology. fProfessor, Department of Radiology. 7116136984
Table I. Initial site of tumor Site
Major salivary gland Parotid Submandibular Sublingual Minor salivary gland Tongue Oral floor Palate Cheek Others Maxillary sinus and nasal cavity Eye Larynx External acoustic Meatus
No. of eases (recurrent)
12 (4) 5 6 (4) 1 20 (3) 3 2 13 (3) 2 9 (1) 4
2 (1) 2 1
External radiation therapy was given by means of a cobalt 60 unit. Beam direction techniques used wedge filtration and one to three fields. Two of the tumors of the tongue were treated with a combination of external radiotherapy and brachytherapy. When only radiation therapy was applied, the radiation dose was 50 to 55 Gy in 16 fractions until 1977; after 1977 the dosewas changed to 65 Gy in 26 fractions. When both radiation therapy and surgery were used, the doseof radiation ranged from 40 to 70 Gy, determined 251
Hosokawa et al.
ORAL SLKG OKX
i i i i .-.-.-.
0 0 Fig.
Treatment Radiation alone Radiation with surgery
n = 33
1. Survival curve for adenoid cystic carcinoma. Table III. Metastasis of tumor
of tumor location and treatment for primary cases ~
recurrent cases -.-.-.-.-.-.-.-.-.-.. -.-.-.-.-.-.-.-.-.-_
Table II. Correlation
Major salivary gland
Minor salivary gland I IO
Other 0 8
by clinical assessment. Table II shows that tumor location determined which treatment was necessary; therefore, the cases were divided into groups by site and analyzed with the Logrank test for curves (p < 5%). RESULTS
The 5-year survival rate in general was 57.9%; however, it was 37.5% for recurrent lesions. Prognosis for recurrent cases was relatively poor. The 5-year survival rate in cases of primary lesions was 64.5% (Fig. 1). The survival rate curves for primary cases of ACC were found to be dependent on the initial site of the disease as shown in Fig. 2. Although no significant differences were proven, the prognosis of cases that involved the major salivary glands appeared to be relatively better than for those with lesions of the minor salivary glands. Hence, we suspect the site of origin might be a factor in prognosis. To further analyze the data to investigate this assumption, differences in sex, age, and regional lymph node metastasis between the “with surgery” and the “without surgery” groups were examined. All patients with lesions of the major
28 (6) 11 (1) 2 (1)
N = nodes. M = metastasis.
salivary glands received a combination of radiation therapy and surgery (Table II). No difference was found between the two treatment groups in relation to patient sex, patient age, or regional lymph node metastases. In the cases of ACC that affected the minor salivary glands, there was no difference in the control rate between those treated with a combination of surgery and radiotherapy and those who received only radiation treatment (Fig. 3). For minor salivary gland lesions, Fig. 4 shows the correlation between tumor size and tumor control. Local control was successful with the use of radiation therapy alone for Tl and T2 cases; however, T3 and T4 cases showed a higher control rate when surgery was also used. The control rate for primary and recurrent cases is shown in Fig. 5. Control was achieved in 73.2% at 5 years for cases of primary lesions. Recurrent lesions had a reduced duration for a disease-free survival rate, and distant metastases were seen earlier in these cases. The average time interval before distant metastasis for recurrent lesions was 10 months, compared with 40 months for primary lesions. The lung
ACC treated by radiotherapy
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i A.-A.-.-.+ i i minor salivary i i._._._._._,_._. -.,.-.-.-.A.-.-.-.-.,., others
2. Survival curve for initial sites of primary lesions.
i i .-.-. -.-.-.A-., with
n = 10
i.-. A--.,.-.-iLLAl.,.-.-.-.-.-.-.-.-.-.-,-.-. I DD
Fig. 3. Control rates related to applied treatment in minor salivary gland primary lesions.
was the most frequent site for distant metastases (78.5%). The survival rates both with and without regional lymph node metastases in cases of primary lesions showed no significant prognostic difference. DISCUSSION
ACC tends to grow slowly and has been considered a relatively benign tumor.* However, destructive behavior has also been reported for ACC.‘, 3,4 The prognosis is poor because of the tendency for local recurrence after treatment and ultimate metastatic
spread. Local recurrence and metastases may not appear until 10 to 1.5 years after the initial treatment. Many authors have concluded recently that radiation therapy controls the primary ACC lesion as effectively as surgery. 5-12Our results revealed a control rate of 73.2% over 5 years for primary lesions. In this report, the prognosis for patients with ACC of major salivary glands appears better than for those who have ACC of the minor salivary glands; however, this could not be proven statistically. The finding of a better prognosis for ACC in major salivary glands is similar to previously reported studies.’ l-l4 That there
ORAL SURGORAL MED ORAL PATHOL August 1992
Hosokawa et al.
i primary I I II I i
n = 33 I
i .-.-.C.-.-.-.-.-.-.-.-, i recurrent (LR) n=8 -.-.-.-.-.-.-.-.-.-.-.-.* recurrent
Fig. 4. Control rates related to tumor size in minor salivary gland primary lesions.
I * i i
1-i .-.-. L-L
T 1, T2
- .-.-.-. .-.-.-.
1 n = 6
A1A ._.-.-.m-.-.-.-.-.-.-.-.-.. &.-.I T3,
g 2 tn
Fig, 5. Control (LR) and disease-free survival (OF) for primary cases and recurrent lesions.
was no difference in the control rates for casesof minor salivary gland, whether patients were treated with surgery as well as radiotherapy, may be due to the difficulties of obtaining a sufficiently wide surgical margin. Primary lesion control is probably best achieved with radiotherapy, even for small ACCs. This agreeswith the findings of Ellis,‘O who also stated that early-stage minor salivary gland tumors were controlled equally well with radiation therapy alone or with radiation combined with surgery. In spite of local tumor control, the disease-freesurvival rate for cases with primary lesions was only
43.9% at 5 years and 20.8% at 10 years. It seemsthat lung metastasis in the late stage decided the prognosis. We believe that radiation therapy is effective in the local control of ACC and contributes to the quality of life for patients. We are obliged to note, however, that there is no effective therapy for metastatic lesions of ACC at present. REFERENCES 1. Conley J, Dingman DL. Adenoid cystic carcinoma in the head and neck (cylindroma). Arch Otolaryngol 1974;1003 l-90.
ACC treated by radiotherapy
Volume 74 Number 2 2. Foote FW Jr, Frazell EL. Tumors of the major salivary glands. 3.
4. 5. 6. 7.
Cancer 1953;6:1065-133. Leafstedt SW, Gaeta JF, Sako K, et al. Adenoid cystic carcinoma of major and minor salivary glands. Am J Surg 1971; 122:756-62. Seaver PR, Kuehn PG. Adenoid cystic carcinoma of the salivarv elands. Am J Sura 1979:137:449-55. Fu KI?, Leibel SA, Leviie ML; et al. Carcinoma of the major and minor salivary glands. Cancer 1977;40:2882-90. Vikram B, Strong EW, Shah JP, et al. Radiation therapy in adenoid-cvstic carcinoma. Int J Radiat Oncol Biol Phvs 1984; 10:221-3.Simpson JR, Thawley SE, Matsuba HM. Adenoid cystic salivary gland carcinoma: treatment with irradiation and surgery. Radiology 1984;151:509-12. Miglianico L, Eschwege F, Marandas P, et al. Cervico-facial adenoid cystic carcinoma: study of 102 cases-influence of radiation theranv. Int J Radiat Oncol Biol Phvs 1987:13:673-g. Matsuba HM:Spector GJ, Thawley SE, et al. Adenoid cystic salivary gland carcinoma. Cancer 1986;57:519-24.
10. Ellis ER, Million RR, Mendenhall WM, et al. The use of radiation therapy in the management of minor salivary gland tumors. Int J Radiat Oncol Biol Phys 1988;15:613-7. 11. Cowie VJ, Pointon RCS. Adenoid cystic carcinoma of the salivary glands. Clin Radio1 1984;35:331-3. 12. Ampil FL, Misra RP. Factors influencing survival of patients with adenoid cystic carcinoma of the salivary glands. J Oral Maxillofac Surg 1987;45:1005-10. 13. Ranger D, Thackray AC, Lucas RB. Mucous gland turnours. Br J Cancer 1956;10:1-16. 14. Hamper K, Lazar F, Dietel M, et al. Prognostic factors for adenoid cystic carcinoma of the head and neck: a retrospective evaluation of 96 cases.J Oral Path01 Med 1990;19:101-7. Reprint requests:
Yoichiro Hosokawa, DDS, PhD Hokkaido University School of Dentistry Nishi 7-chrome, Kita 13-jo, Kita-ku Sapporo 060, Japan