Adenoid Cystic Carcinoma: Factors Influencing Survival
Ronald H. Spiro, MD, New York, New York Andrew G. Huvos, MD, New York, New York Elliot W. Strong, MD, New York, New York
It is perhaps fortunate that only about 10 per cent of all salivary neoplasms are adenoid cystic carcinoma. Many remain unaware that this most common malignant tumor of submaxillary and minor salivary glands usually extends well beyond visible and palpable limits. Experienced clinicians realize that observation must be extended well beyond the customary 5 year interval in order to appreciate how few are cured. Enhanced local control will probably require more extensive initial surgery, postoperative irradiation, adjunctive chemotherapy, or a combination of these modalities. Before these alternatives can be properly assessed by prospective studies in cooperating hospitals, we should be able to select the patients who need the most aggressive therapy. Our experience contradicts other reports which suggest that histologic grading offers a valuable prognostic guide [1,2]. In this study we present additional data to support our contention that clinical findings are far more reliable. Material and Methods The tumor registry of Memorial Sloan-Kettering Cancer Center includes 308 patients with adenoid cystic carcinoma of salivary origin who were seen between 1939 and 1968. After review of the charts and all available slides, 44 patients were excluded either because they were not treated at our hospital or adequate histologic documentation was lacking. Most of the 264 patients included in this study have been reported on previously [3].
From the Head and Neck Service, Department of Surgery, and the Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York. Reprint requests shoukf be addressed to RowId H. Spiro, MD, 1275 York Avenue, New York, New York 10021. Presented at the Twenty-Fifth Annual Meeting of The Society of Head and Neck Surgeons, Pittsburgh, Pennsylvania, April 1-4, 1979.
Volume 138. October 1979
Two thirds of the patients (175) had tumors arising in the mucous glands of the upper aerodigestive tract. The parotid or submaxillary glands were involved in 45 and 41 patients, respectively, and sublingual gland origin was suspected in 3 others. The latter patients are arbitrarily included with those who had primary tumors in the floor of the mouth because we are not certain of the origin of the tumors and the treatment is the same. The distribution of the tumors according to the site of origin is listed in Table I. Almost half of the patients had received previous treatment elsewhere. Both sexes were equally represented. The patients’ ages ranged from 20 to 84 years, with a median age of 52 years. The median age was 43 years when the primary was in the parotid gland and 53 years when the tumor arose elsewhere. After a blind, retrospective review of all available slides, the tumors were divided into three groups according to histologic criteria that have been described [3]. Sixty-two per cent of the patients (164) had grade 1 tumors, whereas 31 and 7 per cent had grades 2 and 3 tumors, respectively. The distribution of tumors according to histologic grade was not influenced by previous treatment or the site of origin. Previously untreated patients with parotid or submaxillary gland primaries were retrospectively staged according to criteria we previously proposed [4,5]. In patients with minor salivary tumors, the staging conforms with the recommendations of the Joint Committee on Staging for squamous carcinoma in similar sites [6]. Of 136 previously untreated patients, 38, 44, and 22 had stage 1, 2, and 3 disease, respectively. Only seven patients had a stage 4 tumor. Fifteen of the 25 patients lacking adequate information for staging had a sinus primary. Treatment was surgical in all but 18 patients (7 per cent). Irradiation or chemotherapy was palliative initial treatment in 16 and 2 patients, respectively, who had unresectable primary tumors or extensive distant metastases. Conservative excision was often possible when the primary tumor arose in the parotid or submaxillary glands or the
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mouth. Radical extirpation, usually including adjacent bone, was the rule when the lesion arose in or near the sinuses (Table II). Conventional radical neck dissection was usually reserved for patients who had clinical evidence of lymph node metastasis, but was occasionally performed electively to facilitate resection of a bulky mouth or submaxillary gland primary. All patients were eligible for at least a 10 year follow-up and results are presented either as “cure” or “survival” rates. Absolute “cure” rates compare the number of patients who are alive and free of disease during the interval in question to the total number eligible for follow-up, assuming that all others succumbed to their tumor. A more relevant “net” or “determinate cure” rate was derived by excluding all who were disease-free when they either died of other causes or were lost to follow-up. Actuarial survival rates were calculated according to the life table method [7]
TABLE I
Distribution of Tumors According to the Site of Origin
Site of Origin
Primary
Palate Parotid gland Submaxillary gland Antrum Tongue Nasal cavity Cheek and lips Gingivae Floor of the mouth Larynx Tonsil Ethmoid Nasopharynx
27 25 25 13 9 11 5 5 6
Total
..
1
66 45 41 31 26 16 11 10 9’ 3 2 1 1
136
126
264
16 16 19 5 6 5 3 3 1 1
Total
Previously Treated
. 1
..
Per cent 25.0 17.0 15.5 11.7 10.6 6.1 4.2 3.6 3.4 1.1 0.6 0.4 0.4 100.0
using a computer program that included Breslow [8] and Mantel-Cox [9] tests of statistical significance in survival patterns between two or more subgroups. Results
Ifi Figure 1, “cure” and survival rates are plotted for the entire group. The survival rate dropped from 69 per cent at 5 years to only 22 per cent at 20 years. Whereas 35 per cent of patients remained diseasefree 5 years after treatment, only 11 per cent had no evidence of tumor 20 years later. Local treatment failure occurred in 74 per cent of patients with minor salivary tumors and 63 per cent of those with parotid or submaxillary tumors, for an overall incidence of 70 per cent. Accurate information regarding the disease-free interval after initial therapy in our hospital was available in 82 of 136 previously untreated patients. Recurrence or spread of tumor was evident within 1 year in 51 patients (62 per cent) and within 5 years in a total of 76 patients (93 per cent). Although survival was occasionally prolonged, the disease-free interval exceeded 5 years in only six patients (7 per cent). This group included one remarkable patient who developed local recurrence 17 years after a maxillectomy for a nasal cavity tumor. Enlarged cervical lymph nodes contained metastatic tumor in 22 patients, and occult metastasis was confirmed in 7 others after elective neck dissection. Regional node involvement developed in a total of 49 patients (19 per cent), including 19 patients in whom neck disease developed subsequently and 1 patient
‘Includes three sublingual gland tumors.
TABLE II
Actuarial survival _-__ Net
Treatment Site of Tumor Antrum, Nasal Submaxiiiary Parotid Cavity, or Larynx Gland Gland
Treatment
Mouth
Conservative excision Radical excision Irradiation
44’
3
27
27
76
46
9
14
6
3
3
4
Chemother-
..
...
2
..
126
52
41
45
22
3
22
8
w
Neck dissection initially
580
Total 101 (38%) 145 (55%) 16 (6%) Fl%,
Total
l
“cure”
includes three sublingual gland tumors.
264 (100%) 55 (21%)
u-
10
15
20
Years
Figure 1. The actuarial survival rate and net cure rate for all patients studied.
The American Journal of Surgery
Adenoid Cystic Carcinoma
in whom a cervical metastasis was excised before he was seen in our hospital. Distant metastasis was documented in at least 114 patients (43 per cent). This is undoubtedly a low estimate because follow-up information was incomplete in some instances and few who died had a postmortem examination. The lungs were most often involved (91 patients; 70 per cent), and median survival after the appearance of distant metastases exceeded 6 years. Although more than one fifth of the patients lived from 5 to as long as 14 years, one third died less than 2 years after distant metastasis was confirmed. The survival time was similar in nine patients whose primary tumors were treated despite evidence of pulmonary metastases when first seen in our hospital (Figure 2). The influence of various factors on determinate “cure” is summarized in Table III. Trends suggesting slightly better cure rates in primary cases, women, and patients older than age 50 years were not supported by statistical analysis of survival data. In contrast, net cure and actuarial survival were significantly lower in patients with submaxillary gland tumors and worst in those with antral primaries. Forty-six per cent of the latter were alive 5 years after treatment, but only 15 per cent had no evidence of disease.
TABLE
III
Factors
Influencing
Net “Cure”
Age 549 years >50 years Sex Men Women Site of origin Palate Parotid gland Submaxillary gland Antrum Tongue Histologic grade Grade 1 Grade 2 Grade 3 Clinical stage Stage 1 Stage 2 Stage 3 Unstaged
q
12
3
4
5
6
Metastasis present lnlllally (9
patIentsI
7
8
910
Years Figure 2. Survival in 97 pafients with distant pulmonary metastasis. (Data on 23 other patients with documented distanf metastasis were incomplete. )
Rate 20 Years
15 Years
10 Years
5 years PtS.
%
PtS.
%
No. Pts.
264
34.6
264
20.4
224
13.1
167
10.5
136 128
41.4 27.8
136 128
23.6 18.2
120 104
13.7 12.5
94 73
10.6 10.3
119 145
31.3 37.4
119 145
17.3 23.2
98 126
12.2 13.9
80 87
13.5 7.2
131 133
35.2 34.1
131 133
17.9 22.8
109 115
10.0 15.8
75 92
6.3 13.8
66 45 41 32 28
36.5 41.9 23.1 15.6 48.1
66 45 41 32 28
28.3 25.0 13.5 3.2 20.0
60 33 35 27 25
14.3 17.2 6.5 3.7 19.0
43 25 26 21 21
15.1 17.4 4.3 0.0 11.8
165 80 19
34.6 32.5 44.4
165 80 19
19.3 19.2 35.3
151 63 10
14.0 9.3 25.0
116 43 8
11.0 8.1 14.3
38 44 22 25
70.6 42.5 22.7 32.0
38 44 22 25
53.6 16.7 9.5 13.6
33 39 20 25
25.0 15.2 5.6 8.0
23 33 17 18
33.3 7.7 6.3 0.0
No.
All patients Previous treatment Primary Previously treated
Similarly, analysis based on retrospective clinical staging yielded differences in cure and survival rates that appeared to be highly significant (Figure 3). For example, survival at 10 years ranged from 72 to 42 to 29 per cent depending on whether the tumor was
No.
No. %
Pk..
%
No. Pts. = number of patients.
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1979
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