Abstract
Purpose
To report outcomes in patients treated with postoperative radiotherapy for nonadenoid cystic carcinomas of the major salivary glands.
Materials and Methods
From 1998–2011, 37 patients with nonadenoid cystic carcinomas of the major salivary gland underwent postoperative radiotherapy. The median radiation dose was 60 Gy (range, 45–70 Gy). TNM distribution included T1–2 (n = 16, 44%), T3–T4 (n = 21, 56%), N0 (n = 19, 51%), and N + (n = 18, 49%). Histologies included adenocarcinoma (n = 13, 35%), squamous cell carcinoma (n = 8, 22%), mucoepidermoid carcinoma (n = 8, 22%), and other (n = 8, 21%). Median follow-up was 4.7 years for all patients (range, 0.3–14.1 years) and 5.0 years for living patients (range, 1.2–12.2 years).
Results
Five-year local-regional control, overall survival (OS), and cancer-specific survival (CSS) were 97%, 76%, and 84%. On univariate analysis, OS was significantly worse for patients ≥ 65 years old (p = 0.04). CSS was significantly worse for positive perineural invasion (p = 0.02), extraparenchymal extension (p = 0.04), and in patients who received no chemotherapy (p = 0.02). Doses > 60 Gy was significantly worse for OS (p = 0.003) and CSS (p = 0.003), although these patients had higher TNM (> T2, p = 0.01) and trended towards a higher rate of extraparenchymal extension (p = 0.08). Four patients (11%) developed ≥ grade 2 toxicities; 3 patients developed early toxicities and one patient developed late toxicities.
Conclusions
Radiotherapy for salivary gland tumors provides excellent local-regional control when combined with surgery. Distant metastasis is the predominant pattern of failure, although chemotherapy seemed to improve cancer-specific survival.
1
Introduction
Salivary gland cancers are uncommon, accounting for less than 1% of all cancers and 3% of all head and neck cancers diagnosed annually in the United States . Approximately 70% to 80% of major salivary gland neoplasms originate in the parotid gland, with the rest originating in the submandibular and sublingual glands . Malignant major salivary glands are a heterogeneous group of tumors with considerable variability in their natural histology and biological behavior. Due to their rarity and histologic variability, these tumors present significant diagnostic and management challenges.
The primary treatment approach for localized tumors is surgical resection. Patients with benign or low-grade tumors are typically treated with surgery alone, while patients with high-grade carcinomas and high-risk features are treated with surgery followed by postoperative radiotherapy (RT) to improve local-regional control. Indications for adjuvant RT include the presence of adverse pathologic features such as positive surgical margins, high-grade histology, perineural invasion, or lymphatic spread . Patients with inoperable disease typically receive definitive RT alone or chemoradiotherapy.
The purpose of this retrospective study is to analyze patient characteristics, pathologic features, and treatment outcomes of nonadenoid cystic carcinomas of the major salivary glands treated with postoperative RT at our institution, and report disease outcomes and toxicity with a focus on patterns of failure. Adenoid cystic carcinomas were excluded from this study because they have a unique natural history.
2
Materials and methods
2.1
Patients
Under an institutional review board-approved protocol, we retrospectively analyzed the medical records of 37 patients with nonadenoid cystic carcinomas of the major salivary glands treated with postoperative RT at Stanford University between March 1998 and April 2011. Patients were excluded if they were treated with palliative intent, had adenoid cystic carcinoma histology, or were medically inoperable. Table 1 details the patient characteristics, pathologic findings, and treatment modalities in this population. The primary sites were as follows: parotid gland (n = 34; 92%) and submandibular gland (n = 3; 8%). The median age of the patients at diagnosis was 67 years (range, 30–94 years). Patients were retrospectively staged according to the 2002 American Joint Committee on Cancer (AJCC) staging system . The median follow-up time was 4.7 years for all patients (range, 0.3–14.1 years) and 5.0 years for living patients (range, 1.2–12.2 years).
| Characteristic | Total patients (%) (n = 37) | |
|---|---|---|
| Age | ≤ 65 years | 19 (51%) |
| > 65 years | 18 (49%) | |
| Gender | Male | 23 (62%) |
| Female | 14 (38%) | |
| Ethnicity | Caucasian | 34 (92%) |
| Asian | 3 (8%) | |
| Location | Parotid Gland | 34 (92%) |
| Submandibular Gland | 3 (8%) | |
| Histology | Adenocarcinoma | 13 (35%) |
| Squamous cell carcinoma | 8 (22%) | |
| Mucoepidermoid carcinoma | 8 (22%) | |
| Poorly differentiated carcinoma | 3 (8%) | |
| Malignant mixed tumor | 5 (13%) | |
| Pathological T stage | 1 | 5 (14%) |
| 2 | 11 (30%) | |
| 3 | 6 (16%) | |
| 4 | 15 (40%) | |
| Pathological N stage | Negative | 19 (51%) |
| Positive | 18 (49%) | |
| Largest Dimension of Tumor | ≤ 2.5 cm | 20 (54%) |
| > 2.5 cm | 17 (46%) | |
| Surgery | Superficial Parotidectomy | 9 (24%) |
| With facial nerve preservation | 6 (16%) | |
| With facial nerve sacrifice | 3 (8%) | |
| Total Parotidectomy | 25 (68%) | |
| With facial nerve preservation | 7 (19%) | |
| With facial nerve sacrifice | 18 (49%) | |
| Submandibulectomy | 3 (8%) | |
| Elective Node Dissection | Yes | 13 (35%) |
| No | 24 (65%) | |
| Radiation Modality | Non-IMRT | 18 (49%) |
| IMRT | 19 (51%) | |
| Surgical Margin | Positive (within 3 mm of tumor) | 29 (77%) |
| Negative (greater than 3 mm) | 7 (20%) | |
| Unknown | 1 (3%) | |
| RT Dose | ≤ 60 Gy | 24 (65%) |
| > 60 Gy | 12 (32%) | |
| Unknown | 1 (3%) | |
| Concurrent Chemotherapy | Yes | 9 (24%) |
| No | 28 (76%) |
2.2
Surgery
All patients were evaluated by a surgeon to determine the feasibility of surgical resection. Nine patients received superficial parotidectomy (24%), 25 patients received total parotidectomy (68%), and 3 patients received submandibulectomy (8%). The facial nerve was sacrificed in 21 patients (57%) and preserved in 13 patients (35%). The breakdown of surgeries is described in Table 1 . Margin status was defined as positive (less than 3 mm from the tumor) or negative (greater than 3 mm away from the tumor) as validated by Brandwein et al . Seven patients had negative margins (20%), 29 patients had positive margins (77%), and 1 patient had unknown margin status (3%). The median tumor size on pathologic report was 2.5 cm (range, 0.5–8 cm). The median time interval from the date of surgery to the start of postoperative RT was 46 days (range, 20–91 days).
2.3
Radiotherapy
Postoperative RT was delivered with 4- or 6-MV photons with a linear accelerator. The RT volume included the primary tumor bed and pathologically involved regional lymph nodes with adequate margins. None of the patients received intraoperative RT or brachytherapy.
The median dose for all patients was 60 Gy (range, 46–70 Gy) in 15 to 35 fractions (median, 30 fractions). Eighteen patients (49%) received 3-dimensional conventional RT (3DCRT) and 19 patients (51%) received intensity-modulated RT (IMRT). The median 3DCRT dose was 58 Gy (range, 46–66 Gy) in 23 to 33 fractions (median, 29 fractions); the median IMRT dose was 60 Gy (range, 58–70 Gy) in 29–35 fractions (median, 30 fractions). The median overall radiation treatment time span for all patients was 42 days (range, 30–73 days).
2.4
Chemotherapy
Chemotherapy was administered at the discretion of the treating medical oncologist based on tumor histology and high-risk features. Nine patients (24%) received concurrent chemotherapy with the following regimens: cisplatin only (n = 4), cetuximab (n = 3), cisplatin/5-fluorouracil (n = 1), and imatinib (n = 1). Histologies for patients receiving chemotherapy were as follows: adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), high grade carcinoma (n = 3), and malignant mixed tumor (n = 1).
2.5
Statistics
Statistical analysis was conducted via SAS version 9.3 (SAS Institute, Cary, NC). To identify independent predictors of disease outcomes, p-values and hazard ratio (HRs) were calculated via the method of Kaplan and Meier and univariate Cox regression analysis, respectively . Overall survival (OS) was defined as the interval between the radiation start date and the date of death from any cause. Cancer-specific survival (CSS) was defined as the interval between the radiation start date and the date of death with active cancer. Freedom from recurrence (FFR) was defined as the interval between the radiation start date and the date of the first recurrence (local-regional or distant). All HRs are reported with 95% Wald confidence intervals.
Complications during or after RT were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Early complications were defined as appearing within 3 months of initiation of RT, whereas late complications were defined as developing > 3 months after initiation of RT.
2
Materials and methods
2.1
Patients
Under an institutional review board-approved protocol, we retrospectively analyzed the medical records of 37 patients with nonadenoid cystic carcinomas of the major salivary glands treated with postoperative RT at Stanford University between March 1998 and April 2011. Patients were excluded if they were treated with palliative intent, had adenoid cystic carcinoma histology, or were medically inoperable. Table 1 details the patient characteristics, pathologic findings, and treatment modalities in this population. The primary sites were as follows: parotid gland (n = 34; 92%) and submandibular gland (n = 3; 8%). The median age of the patients at diagnosis was 67 years (range, 30–94 years). Patients were retrospectively staged according to the 2002 American Joint Committee on Cancer (AJCC) staging system . The median follow-up time was 4.7 years for all patients (range, 0.3–14.1 years) and 5.0 years for living patients (range, 1.2–12.2 years).
| Characteristic | Total patients (%) (n = 37) | |
|---|---|---|
| Age | ≤ 65 years | 19 (51%) |
| > 65 years | 18 (49%) | |
| Gender | Male | 23 (62%) |
| Female | 14 (38%) | |
| Ethnicity | Caucasian | 34 (92%) |
| Asian | 3 (8%) | |
| Location | Parotid Gland | 34 (92%) |
| Submandibular Gland | 3 (8%) | |
| Histology | Adenocarcinoma | 13 (35%) |
| Squamous cell carcinoma | 8 (22%) | |
| Mucoepidermoid carcinoma | 8 (22%) | |
| Poorly differentiated carcinoma | 3 (8%) | |
| Malignant mixed tumor | 5 (13%) | |
| Pathological T stage | 1 | 5 (14%) |
| 2 | 11 (30%) | |
| 3 | 6 (16%) | |
| 4 | 15 (40%) | |
| Pathological N stage | Negative | 19 (51%) |
| Positive | 18 (49%) | |
| Largest Dimension of Tumor | ≤ 2.5 cm | 20 (54%) |
| > 2.5 cm | 17 (46%) | |
| Surgery | Superficial Parotidectomy | 9 (24%) |
| With facial nerve preservation | 6 (16%) | |
| With facial nerve sacrifice | 3 (8%) | |
| Total Parotidectomy | 25 (68%) | |
| With facial nerve preservation | 7 (19%) | |
| With facial nerve sacrifice | 18 (49%) | |
| Submandibulectomy | 3 (8%) | |
| Elective Node Dissection | Yes | 13 (35%) |
| No | 24 (65%) | |
| Radiation Modality | Non-IMRT | 18 (49%) |
| IMRT | 19 (51%) | |
| Surgical Margin | Positive (within 3 mm of tumor) | 29 (77%) |
| Negative (greater than 3 mm) | 7 (20%) | |
| Unknown | 1 (3%) | |
| RT Dose | ≤ 60 Gy | 24 (65%) |
| > 60 Gy | 12 (32%) | |
| Unknown | 1 (3%) | |
| Concurrent Chemotherapy | Yes | 9 (24%) |
| No | 28 (76%) |
2.2
Surgery
All patients were evaluated by a surgeon to determine the feasibility of surgical resection. Nine patients received superficial parotidectomy (24%), 25 patients received total parotidectomy (68%), and 3 patients received submandibulectomy (8%). The facial nerve was sacrificed in 21 patients (57%) and preserved in 13 patients (35%). The breakdown of surgeries is described in Table 1 . Margin status was defined as positive (less than 3 mm from the tumor) or negative (greater than 3 mm away from the tumor) as validated by Brandwein et al . Seven patients had negative margins (20%), 29 patients had positive margins (77%), and 1 patient had unknown margin status (3%). The median tumor size on pathologic report was 2.5 cm (range, 0.5–8 cm). The median time interval from the date of surgery to the start of postoperative RT was 46 days (range, 20–91 days).
2.3
Radiotherapy
Postoperative RT was delivered with 4- or 6-MV photons with a linear accelerator. The RT volume included the primary tumor bed and pathologically involved regional lymph nodes with adequate margins. None of the patients received intraoperative RT or brachytherapy.
The median dose for all patients was 60 Gy (range, 46–70 Gy) in 15 to 35 fractions (median, 30 fractions). Eighteen patients (49%) received 3-dimensional conventional RT (3DCRT) and 19 patients (51%) received intensity-modulated RT (IMRT). The median 3DCRT dose was 58 Gy (range, 46–66 Gy) in 23 to 33 fractions (median, 29 fractions); the median IMRT dose was 60 Gy (range, 58–70 Gy) in 29–35 fractions (median, 30 fractions). The median overall radiation treatment time span for all patients was 42 days (range, 30–73 days).
2.4
Chemotherapy
Chemotherapy was administered at the discretion of the treating medical oncologist based on tumor histology and high-risk features. Nine patients (24%) received concurrent chemotherapy with the following regimens: cisplatin only (n = 4), cetuximab (n = 3), cisplatin/5-fluorouracil (n = 1), and imatinib (n = 1). Histologies for patients receiving chemotherapy were as follows: adenocarcinoma (n = 3), squamous cell carcinoma (n = 2), high grade carcinoma (n = 3), and malignant mixed tumor (n = 1).
2.5
Statistics
Statistical analysis was conducted via SAS version 9.3 (SAS Institute, Cary, NC). To identify independent predictors of disease outcomes, p-values and hazard ratio (HRs) were calculated via the method of Kaplan and Meier and univariate Cox regression analysis, respectively . Overall survival (OS) was defined as the interval between the radiation start date and the date of death from any cause. Cancer-specific survival (CSS) was defined as the interval between the radiation start date and the date of death with active cancer. Freedom from recurrence (FFR) was defined as the interval between the radiation start date and the date of the first recurrence (local-regional or distant). All HRs are reported with 95% Wald confidence intervals.
Complications during or after RT were scored according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE), version 4.0. Early complications were defined as appearing within 3 months of initiation of RT, whereas late complications were defined as developing > 3 months after initiation of RT.
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
