ORIGINAL ARTICLE
Nineteen-year oncologic outcomes and the benefit of elective neck dissection in salivary gland adenoid cystic carcinoma So-Yoon Lee, MD,1 Bo Hwan Kim, PhD,2 Eun Chang Choi, MD, PhD3* 1
Department of Otorhinolaryngology Head and Neck Surgery, The Catholic University of Korea, College of Medicine, Seoul, Korea, 2Department of Nursing, College of Nursing, Gachon University, Inchon, Korea, 3Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
Accepted 24 October 2013 Published online 3 April 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23537
ABSTRACT: Background. The purposes of this study were to evaluate the oncologic outcomes of salivary gland adenoid cystic carcinoma (ACC) and to confirm the benefits of elective neck dissection. Methods. We reviewed the records of 61 consecutive patients with ACC. Surgery was performed in all patients. Results. The occult metastasis rate was 15.38% (4 of 26 patients) and no regional recurrence in the elective neck dissection group was identified. Among 4 clinically node positive (cN1) patients, regional metastasis was identified in 3 through therapeutic neck dissection. Regional recurrence was identified in 4 patients (4 of 31) who had never undergone elective neck treatment of clinically node negative (cN-) status, exclusively. Overall regional metastases (overall N1) were identified in
INTRODUCTION Adenoid cystic carcinoma (ACC) is a rare neoplasm characterized by frequent local recurrence and distant metastasis. Most studies of ACC have focused on its distant metastasis.1 However, regional metastasis has been reported to occur in approximately 4% to 23% of patients with ACC.2–6 Therapeutic neck treatment is usually performed in clinically node positive (cN1) status. Elective neck treatment is recommended only in specific highstage or high-grade tumors and is not generally recommended in all ACCs. However, several recent studies have focused on regional metastasis in ACC, and elective neck treatment (either operation or radiation) has garnered attention as a viable option.3,7–9 The evolution and treatment of ACC is still controversial because its pathogenesis is not completely understood. Controversy exists regarding the most effective treatment for ACC, and there is a lack of reliable information regarding the clinical response of ACC to treatment. The purposes of this study were to evaluate the oncologic outcomes of major and minor salivary gland ACC at a single institution, to identify the relationship between
*Corresponding author: E. C. Choi, Department of Otorhinolaryngology, Yonsei University College of Medicine, 250 Sungsan-ro Seodaemun-gu, Seoul, Korea. E-mail: [email protected]
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11 patients. The overall survival rate was 84.99% at 5 years, 81.13% at 10 and 15 years in (overall N-) status, contrary to 56.82% at 5 years and 28.41% at 10 years in overall N1 status (p 5 .025). Conclusion. Careful follow-up of regional status is important, and proper therapeutic and elective neck treatment can achieve regional control in ACC. Elective neck dissection is recommendable and can provide valuaC 2014 Wiley Periodicals, Inc. ble staging and prognostic information. V Head Neck 36: 1796–1801, 2014
KEY WORDS: adenoid cystic carcinoma, regional metastasis, elective neck dissection, survival, oncologic outcome
regional metastasis and oncologic outcomes, and to confirm the benefits of elective neck dissection in patients with clinically node negative (cN-) status.
PATIENTS AND METHODS We reviewed the records of 61 consecutive patients (23 men and 38 women) with pathologically confirmed ACC in the head and neck area who were treated at a single institution between January 1991 and December 2009. CT, MRI, and/or positron electron transmission imaging were performed before the definitive treatment in all patients. The patient and tumor characteristics are detailed in Table 1. The mean age was 53 years (SD, 10.9; range, 27–85 years). A palpable mass or swelling was the most common presenting symptom. Thirty patients had ACCs in major glands, and 31 patients had ACCs in minor glands. Primary sites were the parotid gland, submandibular gland (SMG), sublingual gland, oral minor salivary gland, and sinonasal minor salivary gland. The distribution of patients with primary ACCs in these glands was 12, 17, 1, 27, and 4, respectively. Tumors were staged using the TNM staging system in accord with the criteria of the American Joint Committee on Cancer for squamous cell carcinoma in each subsite. Stage I to II was found in 36 patients and stage III to IV was found in 25 patients.
ONCOLOGIC
TABLE 1. Patient and tumor characteristics. Characteristic
No. of patients
%*
Sex, M:F Age, y (range)
23:38 53.37 (SD, 10.99)
(range, 27–85)
41 16 2 2 30 31
67.21 26.23 3.28 3.28 49.18 50.82
12 17 1 27 4
19.67 27.87 1.64 44.26 6.56
40 21
65.57 34.43
57 4
93.44 6.56
Symptom Mass or swelling Pain Facial palsy Others (no symptoms, epistaxis) Major gland Minor gland Primary site Parotid gland SMG Sublingual gland Oral Sinonasal tract T classification 1–2 3–4 N classification Negative Positive AJCC stage I–II III–IV Follow-up period, mo
36 59.02 25 40.98 57.98 (range, 15–183) (SD, 38.88)
Abbreviations: SMG, submandibular gland; AJCC, American Joint Committee on Cancer. * Except as otherwise stated.
Patient outcomes were classified as either local recurrence defined as the appearance of the signs and symptoms of malignancy at a primary site that were previously treated and responded to the therapy, regional recurrence defined as the appearance of the signs and symptoms of malignancy at the lymph nodes after initial treatment, or distant metastasis defined as a secondary cancerous growth form by transmission of cancerous cells from a primary growth located to elsewhere in the body. We also analyzed oncologic outcomes using the term “overall regional metastasis” (overall N1), which was composed of pathologically proven regional metastasis through neck dissection either therapeutic or elective at initial treatment plus regional recurrences after initial treatment during follow-up. If indicated, postoperative radiotherapy and/or chemotherapy were performed. The indication for postoperative adjuvant treatment was positive or closed surgical margin status, regional metastasis, perineural invasion, lymphovascular invasion, and/or high stage (III–IV) disease. The time of analysis was from the date of pathologic diagnosis to the date of the final follow-up or death. The mean follow-up period was 57.98 months (SD, 38.88; range, 15–183 months). Patients were fully informed about the treatment. This study was approved by the institutional review board.
Statistics analysis Statistical analyses were performed using the chi-square (or Fisher’s exact) test for correlation evaluation, and
OUTCOMES OF ADENOID CYSTIC CARCINOMA OF THE HEAD AND NECK
curves describing overall and disease-free survival were generated using the Kaplan–Meier product limit method. The statistical significance of differences between actuarial curves was determined using a log-rank test. These analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). P values of < .05 were deemed statistically significant.
RESULTS Treatment and oncologic outcomes are shown in Table 2. Primary surgical treatment was performed in all patients, and there was a 50.82% rate of closed or positive surgical margins. Reconstruction was conducted in 16 patients. Histologic subtype was identified in 41 patients according to the following categories: a mixed pattern of cribriform and tubular, pure cribriform, solid, and pure tubular types. The mixed pattern of cribriform and tubular type was the most common. In 40 patients from whom we had detailed pathologic information, perineural invasion was identified in 25 patients. Lymphovascular invasion was identified in 7 of 38 patients. Postoperative radiotherapy was performed in 50 patients, and neck irradiation was administered to 21 patients. The mean radiation dose was 6113 cGy (SD, 541; range, 4000–6900 cGy).
Locoregional control/distant metastasis During the follow-up period, local recurrence was found in 9 patients (14.75%). The mean latency of recurrence was 28 months (SD, 14.41; range, 7–46 months). In 4 of 9 patients, recurrences were identified in sinonasal minor salivary glands, but the primary site was not a significant factor for local recurrence (p 5 .097). Clinical T4 status was the only factor affecting local recurrence (p 5 .049). All 9 patients underwent salvage treatment, and 3 of them were cured. The salvage rate was 33.3%. A cN1 status was found in 4 patients, and these patients underwent therapeutic neck dissections. In cNstatus, elective neck dissection was performed in 26 of 57 patients. In cN1 patients who underwent therapeutic neck dissection, pathologically proven regional metastasis was found in 3 of 4 patients. Histopathology subtype was cribriform, solid, and mixed cribriform and tubular, respectively. Among the patients who underwent elective neck dissection, 4 of 26 patients had regional metastasis. The occult metastasis rate was 15.38%. Histopathology subtype was 1 cribriform, 2 mixed cribriform and tubular, and the other had no information. Three were minor gland ACCs and 2 had low stage I to II disease. Regional recurrence was identified in 4 patients who were cN- without performing elective neck dissection or elective neck irradiation. The primary sites were the parotid gland, SMG, oral, and sinonasal minor salivary glands, respectively. The histopathology subtypes were cribriform, tubular, and mixed cribriform and tubular, respectively. The rest had no subtype information. Three of them had low stage disease. The mean latency of regional recurrence was 37.5 months (SD, 32.14; range, 10–76 months). Regional recurrence was not identified in cN1 patients who underwent therapeutic neck dissection or in HEAD & NECK—DOI 10.1002/HED
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TABLE 2. Treatment and oncologic results.
Therapeutic neck dissection Elective neck dissection Not applied Applied SOND Regional dissection Level Ib dissection Occult lymph node metastasis (n 5 26) Absent Present Reconstruction Not applied Applied Postoperative radiation therapy Not applied Applied Unknown Sub-histopathology (n 5 43) Mixed pattern Pure cribriform Solid Pure tubular Surgical margin Negative Positive Unknown Perineural invasion (n 5 40) Absent Present Lymphovascular invasion (n 5 38) Absent Present Local recurrence Absent Present Mean latency of local recurrence, mo Regional recurrence Absent Present Mean latency of regional recurrence, mo Distant metastasis Absent Present Mean latency of distant metastasis, mo Survival (survived:dead) NED AWD DOD DWOD Overall N status Negative Positive
TABLE 3. Comparison between overall node positive and overall node negative status. No. of patients (n 5 61)
%
4
6.57
31 26 19 2 5
50.81 42.62 31.14 3.28 8.20
22 4
84.62 15.38
45 16
73.77 26.23
10 50 1
16.4 82.0 1.6
16 14 9 4
37.21 32.56 20.93 9.3
28 31 2
45.90 50.82 3.28
15 25
37.5 62.5
31 7
81.58 18.42
52 85.24 9 14.76 28 (range, 7–46) (SD, 14.41) 57 4 37.5 (SD, 32.14)
93.44 6.56 (range, 10–76)
39 22 33.82 (SD, 24.35) 49:12 38 11 11 1
63.93 36.07 (range, 5–94)
50 11
81.97 18.03
62.3 18.03 18.03 1.64
Abbreviations: SOND, supra-omohyoid neck dissection, neck levels I–III; NED, no evidence of disease; AWD, alive with disease; DOD, death of disease; DWOD, death with other disease.
cN- patients who underwent elective neck treatment. During the follow-up period, overall N1 was identified in 11 patients: 7 pathologically proven regional metastases (3 1798
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No. of overall N1 patients (%) (n 5 11)
No. of overall N2 patients (%) (n 5 50)
Age, y 52.81 (SD, 11.88) 53.5 (SD, 10.9) Sex, M:F 4:7 19:31 Major:minor gland 3:8 (27.3:72.7) 27:23 (54.0:46.0) T classification 1–2 8 (72.7) 32 (64.0) 3–4 3 (27.3) 18 (36.0) AJCC stage I–II 5 (45.5) 31 (62.0) III–IV 6 (54.5) 19 (38.0) Sub-histopathology Mixed pattern 6 (54.5) 10 (20) Pure cribriform 2 (18.2) 12 (24) Solid 1 (9.1) 8 (16) Pure tubular 0 4 (8) Not identified 2 (18.2) 16 (32) Radiation therapy 8 (72.7) 42 (84.0) Local recurrence 4 (36.4) 5 (10.0) Distant metastasis 7 (63.6) 15 (30.0) Survivors 6 (54.5) 43 (86.0) Mean DFS, mo 36.81 (SD, 30.55) 53.20 (SD, 39.87)
p value
.864 .919 .108 .581 .312 .203
.757 .057 .048 .018 .146
Abbreviations: N1, node positive; N-, node negative; AJCC, American Joint Committee on Cancer; DFS, disease-free survival.
actual regional metastases after therapeutic neck dissection and 4 occult metastases after elective neck dissection) and 4 regional recurrences. There were no significant differences in patient or tumor characteristics between major and minor salivary gland ACC, and local and regional recurrence rates were not different. However, the mean latency of regional recurrence was 11.0 months (SD, 1.41) in minor gland ACC, compared with 64.0 months (SD, 16.97) in major gland ACC. Minor gland ACC had a significantly shorter latency of regional recurrence (p 5 .047). Distant metastasis was found in 22 patients (36.07%) who had major gland ACCs (7 of 30 patients; 23.33%) and minor gland ACCs (15 of 31 patients; 48.39%). Distant metastasis was more frequent in minor gland ACCs (p 5 .051). The mean latency of distant metastasis was 33.8 months (SD, 24.3; range, 5–94 months). Distant metastasis occurred most frequently in the lung (19 of 22 patients), followed by the spine, liver, pleura, skin, and brain. Multisite metastases were found in 3 patients. Factors affecting distant metastasis were clinical stage (p 5 .024) and overall N status (p 5 .048). In stage I to II disease, 9 of 36 patients (25%) developed distant metastasis, and in stage III to IV disease, 13 of 25 patients (52%) developed distant metastasis. In overall N-, 15 of 50 patients (30.6%) developed distant metastasis, and 7 of 11 patients (63.64%) developed distant metastasis in overall N1 (Table 3). Of 4 patients with occult metastasis, 3 (75%) developed distant metastasis, compared with 5 of 22 patients (22.7%) without occult metastasis. Half of the patients in the occult metastases group (2 of 4 patients) died of the disease, compared with 0 of 22 patients (0%) without occult metastasis.
ONCOLOGIC
OUTCOMES OF ADENOID CYSTIC CARCINOMA OF THE HEAD AND NECK
FIGURE 1. Kaplan–Meier overall survival curve. (A) The overall survival rate was 79.8% at 5 years, 76.85% at 10 years, and 64.04% at 15 years. (B) Disease-free survival rate was 81.6% at 5 years and 75.78% at 10 and 15 years. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Survival/prognostic factors At the end of the follow-up, 12 of 61 patients had died, 11 of them because of their diseases. The mean survival was 64.3 months (SD, 39.8; range, 15–183 months), and the mean disease-free survival was 50.2 months (SD, 38.6; range, 15–183 months). The overall survival rate was 79.8% at 5 years, 76.85% at 10 years, and 64.04% at 15 years (Figure 1A). The disease-free survival rate was 81.6% at 5 years and 75.78% at 10 and 15 years (Figure 1B). Univariate analysis confirmed pathologically proven regional metastasis (actual regional metastasis after therapeutic neck dissection [p 5 .017] and occult metastasis [p 5 .033]), overall N1 status (p 5 .025), and distant metastasis (p 5 .001) as prognostic factors. The survival rate was 90.26% at 5 years, 85.25% at 10 years, and
FIGURE 2. Kaplan–Meier overall survival curve according to low and high disease stage. Overall survival at 15 years was not significantly different between low- and high-stage disease groups. Patients in the high-stage disease group had lower survival rates at 5 and 10 years (p 5 .138). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
63.93% at 15 years in stage I to II disease and 64.94% at 5, 10, and 15 years in stage III to IV disease. Disease stage was not a prognostic factor. However, the highstage disease groups had a lower survival rate at 5 and 10 years than patients with low-stage disease (p 5 .138; Figure 2). The survival rate was 84.99% at 5 years and 81.13% at 10 and 15 years in patients with overall N- status; however, in patients with overall N1 status, the survival rate was 56.82% at 5 years and 28.41% at 10 years. Patients with overall N1 status had significantly lower survival rates (p 5 .025; Figure 3). We compared elective neck dissection and no elective neck dissection groups in cNpatients to determine whether elective neck dissection was related to oncologic outcomes. There were no
FIGURE 3. Kaplan–Meier overall survival curve according to overall N status. In overall N- status, the overall survival rate was 84.99% at 5 years, 81.13% at 10 and 15 years. In overall N1 status, the overall survival rate was 56.82% at 5 years and 28.41% at 10 years (p 5 .025). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
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TABLE 4. Comparison between alive with disease and no evidence of disease survivors.
Age, y Sex, M:F Major:minor gland T classification 1–2 3–4 N classification Negative Positive AJCC stage I–II III–IV Margin status Negative Positive Unknown Local recurrence Elective neck dissection Overall N1 Distant metastasis Mean survival, mo Mean DFS, mo
No. of AWD patients (%) (n 5 11)
No. of NED patients (%) (n 5 38)
48.73 (SD, 10.04) 5:6 2:9 (18.2:81.8)
53.87 (SD, 12.00) 13:25 24:14 (63.2:36.8)
5 (15.15) 6 (37.50)
28 (84.85) 10 (62.50)
10 (21.27) 1 (50.0)
37 (78.73) 1 (50.0)
4 (12.90) 7 (38.88)
27 (87.10) 11 (61.12)
4 (36.36) 6 (54.54) 1 (9.1) 3 (27.27) 4 (36.36) 2 (18.18) 9 (81.82) 68.0 (SD, 26.61) 28.82 (SD, 15.54)
19 (50.0) 19 (50.0) – 3 (7.89)* 19 (50.0) 4 (10.53)* 2 (5.26)* 69.87 (SD, 43.26) 64.13 (SD, 40.88)
p value
.202 .502 .014 .141 .402 .018 .726
.123 .424 .605
Nineteen-year oncologic outcomes and the benefit of elective neck dissection in salivary gland adenoid cystic carcinoma So-Yoon Lee, MD,1 Bo Hwan Kim, PhD,2 Eun Chang Choi, MD, PhD3* 1
Department of Otorhinolaryngology Head and Neck Surgery, The Catholic University of Korea, College of Medicine, Seoul, Korea, 2Department of Nursing, College of Nursing, Gachon University, Inchon, Korea, 3Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.
Accepted 24 October 2013 Published online 3 April 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI 10.1002/hed.23537
ABSTRACT: Background. The purposes of this study were to evaluate the oncologic outcomes of salivary gland adenoid cystic carcinoma (ACC) and to confirm the benefits of elective neck dissection. Methods. We reviewed the records of 61 consecutive patients with ACC. Surgery was performed in all patients. Results. The occult metastasis rate was 15.38% (4 of 26 patients) and no regional recurrence in the elective neck dissection group was identified. Among 4 clinically node positive (cN1) patients, regional metastasis was identified in 3 through therapeutic neck dissection. Regional recurrence was identified in 4 patients (4 of 31) who had never undergone elective neck treatment of clinically node negative (cN-) status, exclusively. Overall regional metastases (overall N1) were identified in
INTRODUCTION Adenoid cystic carcinoma (ACC) is a rare neoplasm characterized by frequent local recurrence and distant metastasis. Most studies of ACC have focused on its distant metastasis.1 However, regional metastasis has been reported to occur in approximately 4% to 23% of patients with ACC.2–6 Therapeutic neck treatment is usually performed in clinically node positive (cN1) status. Elective neck treatment is recommended only in specific highstage or high-grade tumors and is not generally recommended in all ACCs. However, several recent studies have focused on regional metastasis in ACC, and elective neck treatment (either operation or radiation) has garnered attention as a viable option.3,7–9 The evolution and treatment of ACC is still controversial because its pathogenesis is not completely understood. Controversy exists regarding the most effective treatment for ACC, and there is a lack of reliable information regarding the clinical response of ACC to treatment. The purposes of this study were to evaluate the oncologic outcomes of major and minor salivary gland ACC at a single institution, to identify the relationship between
*Corresponding author: E. C. Choi, Department of Otorhinolaryngology, Yonsei University College of Medicine, 250 Sungsan-ro Seodaemun-gu, Seoul, Korea. E-mail: [email protected]
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11 patients. The overall survival rate was 84.99% at 5 years, 81.13% at 10 and 15 years in (overall N-) status, contrary to 56.82% at 5 years and 28.41% at 10 years in overall N1 status (p 5 .025). Conclusion. Careful follow-up of regional status is important, and proper therapeutic and elective neck treatment can achieve regional control in ACC. Elective neck dissection is recommendable and can provide valuaC 2014 Wiley Periodicals, Inc. ble staging and prognostic information. V Head Neck 36: 1796–1801, 2014
KEY WORDS: adenoid cystic carcinoma, regional metastasis, elective neck dissection, survival, oncologic outcome
regional metastasis and oncologic outcomes, and to confirm the benefits of elective neck dissection in patients with clinically node negative (cN-) status.
PATIENTS AND METHODS We reviewed the records of 61 consecutive patients (23 men and 38 women) with pathologically confirmed ACC in the head and neck area who were treated at a single institution between January 1991 and December 2009. CT, MRI, and/or positron electron transmission imaging were performed before the definitive treatment in all patients. The patient and tumor characteristics are detailed in Table 1. The mean age was 53 years (SD, 10.9; range, 27–85 years). A palpable mass or swelling was the most common presenting symptom. Thirty patients had ACCs in major glands, and 31 patients had ACCs in minor glands. Primary sites were the parotid gland, submandibular gland (SMG), sublingual gland, oral minor salivary gland, and sinonasal minor salivary gland. The distribution of patients with primary ACCs in these glands was 12, 17, 1, 27, and 4, respectively. Tumors were staged using the TNM staging system in accord with the criteria of the American Joint Committee on Cancer for squamous cell carcinoma in each subsite. Stage I to II was found in 36 patients and stage III to IV was found in 25 patients.
ONCOLOGIC
TABLE 1. Patient and tumor characteristics. Characteristic
No. of patients
%*
Sex, M:F Age, y (range)
23:38 53.37 (SD, 10.99)
(range, 27–85)
41 16 2 2 30 31
67.21 26.23 3.28 3.28 49.18 50.82
12 17 1 27 4
19.67 27.87 1.64 44.26 6.56
40 21
65.57 34.43
57 4
93.44 6.56
Symptom Mass or swelling Pain Facial palsy Others (no symptoms, epistaxis) Major gland Minor gland Primary site Parotid gland SMG Sublingual gland Oral Sinonasal tract T classification 1–2 3–4 N classification Negative Positive AJCC stage I–II III–IV Follow-up period, mo
36 59.02 25 40.98 57.98 (range, 15–183) (SD, 38.88)
Abbreviations: SMG, submandibular gland; AJCC, American Joint Committee on Cancer. * Except as otherwise stated.
Patient outcomes were classified as either local recurrence defined as the appearance of the signs and symptoms of malignancy at a primary site that were previously treated and responded to the therapy, regional recurrence defined as the appearance of the signs and symptoms of malignancy at the lymph nodes after initial treatment, or distant metastasis defined as a secondary cancerous growth form by transmission of cancerous cells from a primary growth located to elsewhere in the body. We also analyzed oncologic outcomes using the term “overall regional metastasis” (overall N1), which was composed of pathologically proven regional metastasis through neck dissection either therapeutic or elective at initial treatment plus regional recurrences after initial treatment during follow-up. If indicated, postoperative radiotherapy and/or chemotherapy were performed. The indication for postoperative adjuvant treatment was positive or closed surgical margin status, regional metastasis, perineural invasion, lymphovascular invasion, and/or high stage (III–IV) disease. The time of analysis was from the date of pathologic diagnosis to the date of the final follow-up or death. The mean follow-up period was 57.98 months (SD, 38.88; range, 15–183 months). Patients were fully informed about the treatment. This study was approved by the institutional review board.
Statistics analysis Statistical analyses were performed using the chi-square (or Fisher’s exact) test for correlation evaluation, and
OUTCOMES OF ADENOID CYSTIC CARCINOMA OF THE HEAD AND NECK
curves describing overall and disease-free survival were generated using the Kaplan–Meier product limit method. The statistical significance of differences between actuarial curves was determined using a log-rank test. These analyses were performed using SAS version 9.2 (SAS Institute, Cary, NC). P values of < .05 were deemed statistically significant.
RESULTS Treatment and oncologic outcomes are shown in Table 2. Primary surgical treatment was performed in all patients, and there was a 50.82% rate of closed or positive surgical margins. Reconstruction was conducted in 16 patients. Histologic subtype was identified in 41 patients according to the following categories: a mixed pattern of cribriform and tubular, pure cribriform, solid, and pure tubular types. The mixed pattern of cribriform and tubular type was the most common. In 40 patients from whom we had detailed pathologic information, perineural invasion was identified in 25 patients. Lymphovascular invasion was identified in 7 of 38 patients. Postoperative radiotherapy was performed in 50 patients, and neck irradiation was administered to 21 patients. The mean radiation dose was 6113 cGy (SD, 541; range, 4000–6900 cGy).
Locoregional control/distant metastasis During the follow-up period, local recurrence was found in 9 patients (14.75%). The mean latency of recurrence was 28 months (SD, 14.41; range, 7–46 months). In 4 of 9 patients, recurrences were identified in sinonasal minor salivary glands, but the primary site was not a significant factor for local recurrence (p 5 .097). Clinical T4 status was the only factor affecting local recurrence (p 5 .049). All 9 patients underwent salvage treatment, and 3 of them were cured. The salvage rate was 33.3%. A cN1 status was found in 4 patients, and these patients underwent therapeutic neck dissections. In cNstatus, elective neck dissection was performed in 26 of 57 patients. In cN1 patients who underwent therapeutic neck dissection, pathologically proven regional metastasis was found in 3 of 4 patients. Histopathology subtype was cribriform, solid, and mixed cribriform and tubular, respectively. Among the patients who underwent elective neck dissection, 4 of 26 patients had regional metastasis. The occult metastasis rate was 15.38%. Histopathology subtype was 1 cribriform, 2 mixed cribriform and tubular, and the other had no information. Three were minor gland ACCs and 2 had low stage I to II disease. Regional recurrence was identified in 4 patients who were cN- without performing elective neck dissection or elective neck irradiation. The primary sites were the parotid gland, SMG, oral, and sinonasal minor salivary glands, respectively. The histopathology subtypes were cribriform, tubular, and mixed cribriform and tubular, respectively. The rest had no subtype information. Three of them had low stage disease. The mean latency of regional recurrence was 37.5 months (SD, 32.14; range, 10–76 months). Regional recurrence was not identified in cN1 patients who underwent therapeutic neck dissection or in HEAD & NECK—DOI 10.1002/HED
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TABLE 2. Treatment and oncologic results.
Therapeutic neck dissection Elective neck dissection Not applied Applied SOND Regional dissection Level Ib dissection Occult lymph node metastasis (n 5 26) Absent Present Reconstruction Not applied Applied Postoperative radiation therapy Not applied Applied Unknown Sub-histopathology (n 5 43) Mixed pattern Pure cribriform Solid Pure tubular Surgical margin Negative Positive Unknown Perineural invasion (n 5 40) Absent Present Lymphovascular invasion (n 5 38) Absent Present Local recurrence Absent Present Mean latency of local recurrence, mo Regional recurrence Absent Present Mean latency of regional recurrence, mo Distant metastasis Absent Present Mean latency of distant metastasis, mo Survival (survived:dead) NED AWD DOD DWOD Overall N status Negative Positive
TABLE 3. Comparison between overall node positive and overall node negative status. No. of patients (n 5 61)
%
4
6.57
31 26 19 2 5
50.81 42.62 31.14 3.28 8.20
22 4
84.62 15.38
45 16
73.77 26.23
10 50 1
16.4 82.0 1.6
16 14 9 4
37.21 32.56 20.93 9.3
28 31 2
45.90 50.82 3.28
15 25
37.5 62.5
31 7
81.58 18.42
52 85.24 9 14.76 28 (range, 7–46) (SD, 14.41) 57 4 37.5 (SD, 32.14)
93.44 6.56 (range, 10–76)
39 22 33.82 (SD, 24.35) 49:12 38 11 11 1
63.93 36.07 (range, 5–94)
50 11
81.97 18.03
62.3 18.03 18.03 1.64
Abbreviations: SOND, supra-omohyoid neck dissection, neck levels I–III; NED, no evidence of disease; AWD, alive with disease; DOD, death of disease; DWOD, death with other disease.
cN- patients who underwent elective neck treatment. During the follow-up period, overall N1 was identified in 11 patients: 7 pathologically proven regional metastases (3 1798
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No. of overall N1 patients (%) (n 5 11)
No. of overall N2 patients (%) (n 5 50)
Age, y 52.81 (SD, 11.88) 53.5 (SD, 10.9) Sex, M:F 4:7 19:31 Major:minor gland 3:8 (27.3:72.7) 27:23 (54.0:46.0) T classification 1–2 8 (72.7) 32 (64.0) 3–4 3 (27.3) 18 (36.0) AJCC stage I–II 5 (45.5) 31 (62.0) III–IV 6 (54.5) 19 (38.0) Sub-histopathology Mixed pattern 6 (54.5) 10 (20) Pure cribriform 2 (18.2) 12 (24) Solid 1 (9.1) 8 (16) Pure tubular 0 4 (8) Not identified 2 (18.2) 16 (32) Radiation therapy 8 (72.7) 42 (84.0) Local recurrence 4 (36.4) 5 (10.0) Distant metastasis 7 (63.6) 15 (30.0) Survivors 6 (54.5) 43 (86.0) Mean DFS, mo 36.81 (SD, 30.55) 53.20 (SD, 39.87)
p value
.864 .919 .108 .581 .312 .203
.757 .057 .048 .018 .146
Abbreviations: N1, node positive; N-, node negative; AJCC, American Joint Committee on Cancer; DFS, disease-free survival.
actual regional metastases after therapeutic neck dissection and 4 occult metastases after elective neck dissection) and 4 regional recurrences. There were no significant differences in patient or tumor characteristics between major and minor salivary gland ACC, and local and regional recurrence rates were not different. However, the mean latency of regional recurrence was 11.0 months (SD, 1.41) in minor gland ACC, compared with 64.0 months (SD, 16.97) in major gland ACC. Minor gland ACC had a significantly shorter latency of regional recurrence (p 5 .047). Distant metastasis was found in 22 patients (36.07%) who had major gland ACCs (7 of 30 patients; 23.33%) and minor gland ACCs (15 of 31 patients; 48.39%). Distant metastasis was more frequent in minor gland ACCs (p 5 .051). The mean latency of distant metastasis was 33.8 months (SD, 24.3; range, 5–94 months). Distant metastasis occurred most frequently in the lung (19 of 22 patients), followed by the spine, liver, pleura, skin, and brain. Multisite metastases were found in 3 patients. Factors affecting distant metastasis were clinical stage (p 5 .024) and overall N status (p 5 .048). In stage I to II disease, 9 of 36 patients (25%) developed distant metastasis, and in stage III to IV disease, 13 of 25 patients (52%) developed distant metastasis. In overall N-, 15 of 50 patients (30.6%) developed distant metastasis, and 7 of 11 patients (63.64%) developed distant metastasis in overall N1 (Table 3). Of 4 patients with occult metastasis, 3 (75%) developed distant metastasis, compared with 5 of 22 patients (22.7%) without occult metastasis. Half of the patients in the occult metastases group (2 of 4 patients) died of the disease, compared with 0 of 22 patients (0%) without occult metastasis.
ONCOLOGIC
OUTCOMES OF ADENOID CYSTIC CARCINOMA OF THE HEAD AND NECK
FIGURE 1. Kaplan–Meier overall survival curve. (A) The overall survival rate was 79.8% at 5 years, 76.85% at 10 years, and 64.04% at 15 years. (B) Disease-free survival rate was 81.6% at 5 years and 75.78% at 10 and 15 years. [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
Survival/prognostic factors At the end of the follow-up, 12 of 61 patients had died, 11 of them because of their diseases. The mean survival was 64.3 months (SD, 39.8; range, 15–183 months), and the mean disease-free survival was 50.2 months (SD, 38.6; range, 15–183 months). The overall survival rate was 79.8% at 5 years, 76.85% at 10 years, and 64.04% at 15 years (Figure 1A). The disease-free survival rate was 81.6% at 5 years and 75.78% at 10 and 15 years (Figure 1B). Univariate analysis confirmed pathologically proven regional metastasis (actual regional metastasis after therapeutic neck dissection [p 5 .017] and occult metastasis [p 5 .033]), overall N1 status (p 5 .025), and distant metastasis (p 5 .001) as prognostic factors. The survival rate was 90.26% at 5 years, 85.25% at 10 years, and
FIGURE 2. Kaplan–Meier overall survival curve according to low and high disease stage. Overall survival at 15 years was not significantly different between low- and high-stage disease groups. Patients in the high-stage disease group had lower survival rates at 5 and 10 years (p 5 .138). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
63.93% at 15 years in stage I to II disease and 64.94% at 5, 10, and 15 years in stage III to IV disease. Disease stage was not a prognostic factor. However, the highstage disease groups had a lower survival rate at 5 and 10 years than patients with low-stage disease (p 5 .138; Figure 2). The survival rate was 84.99% at 5 years and 81.13% at 10 and 15 years in patients with overall N- status; however, in patients with overall N1 status, the survival rate was 56.82% at 5 years and 28.41% at 10 years. Patients with overall N1 status had significantly lower survival rates (p 5 .025; Figure 3). We compared elective neck dissection and no elective neck dissection groups in cNpatients to determine whether elective neck dissection was related to oncologic outcomes. There were no
FIGURE 3. Kaplan–Meier overall survival curve according to overall N status. In overall N- status, the overall survival rate was 84.99% at 5 years, 81.13% at 10 and 15 years. In overall N1 status, the overall survival rate was 56.82% at 5 years and 28.41% at 10 years (p 5 .025). [Color figure can be viewed in the online issue, which is available at wileyonlinelibrary.com.]
HEAD & NECK—DOI 10.1002/HED
DECEMBER 2014
1799
LEE ET AL.
TABLE 4. Comparison between alive with disease and no evidence of disease survivors.
Age, y Sex, M:F Major:minor gland T classification 1–2 3–4 N classification Negative Positive AJCC stage I–II III–IV Margin status Negative Positive Unknown Local recurrence Elective neck dissection Overall N1 Distant metastasis Mean survival, mo Mean DFS, mo
No. of AWD patients (%) (n 5 11)
No. of NED patients (%) (n 5 38)
48.73 (SD, 10.04) 5:6 2:9 (18.2:81.8)
53.87 (SD, 12.00) 13:25 24:14 (63.2:36.8)
5 (15.15) 6 (37.50)
28 (84.85) 10 (62.50)
10 (21.27) 1 (50.0)
37 (78.73) 1 (50.0)
4 (12.90) 7 (38.88)
27 (87.10) 11 (61.12)
4 (36.36) 6 (54.54) 1 (9.1) 3 (27.27) 4 (36.36) 2 (18.18) 9 (81.82) 68.0 (SD, 26.61) 28.82 (SD, 15.54)
19 (50.0) 19 (50.0) – 3 (7.89)* 19 (50.0) 4 (10.53)* 2 (5.26)* 69.87 (SD, 43.26) 64.13 (SD, 40.88)
p value
.202 .502 .014 .141 .402 .018 .726
.123 .424 .605
