High-risk Salivary Gland Research Articles

Chemoradiotherapy versus radiotherapy in high risk salivary gland cancer

ObjectiveThe aim of this study was to investigate the potential survival benefits associated with chemoradiotherapy (CRT) as opposed to radiotherapy (RT) in patients with resected high-risk salivary gland cancer (SGC), with a specific focus on determining whether these benefits are influenced by the number of high-risk variables.MethodsPatients who underwent surgical treatment for high-risk SGC were retrospectively enrolled and categorized into either CRT or RT groups. The impact of adjuvant therapy on locoregional control (LRC) and overall survival (OS) was assessed using a multivariable Cox model.ResultsA total of 152 patients were included following propensity score-matching. In comparison to RT, CRT did not demonstrate a significant survival advantage in terms of LRC (p = 0.485, HR: 1.14, 95%CI: 0.36–4.22) and OS (p = 0.367, HR: 0.99, 95%CI: 0.17–3.87) in entire population. But among patients with T3/4 stage, high-grade tumors, and 5 or more positive lymph nodes, the addition of chemotherapy to RT significantly (p = 0.042) correlated with a 15% reduction in the risk of cancer recurrence (95%CI: 4-54%). Conversely, in other subgroups with varying combinations of high-risk variables, CRT did not provide additional survival benefits for LRC and OS compared to RT.ConclusionAdjuvant chemotherapy may be considered in conjunction with RT specifically in cases where there is a presence of T3/4 stage, high-grade tumors, and 5 or more metastatic lymph nodes in high-risk SGC.

A multicenter retrospective analysis of patients with salivary gland carcinoma treated with postoperative radiotherapy alone or chemoradiotherapy

BackgroundThe aim of this study was to interrogate if the use of postoperative chemoradiotherapy (POCRT) correlated with superior oncological outcomes for certain subgroups of patients with high-risk salivary gland carcinoma (SGC), compared with postoperative radiotherapy (PORT) alone. MethodsThis multicenter retrospective study included 411 patients with surgically resected SGC who underwent PORT (n = 263) or POCRT (n = 148) between 2000 and 2015. Possible correlations of clinical parameters with outcomes were examined using the Kaplan-Meier analysis and Cox proportional-hazards regression model. ResultsThe median follow-up of survivors is 10.9 years. For the entire cohort, adding concurrent chemotherapy to PORT was not associated with OS, PFS, or LRC improvement. However, patients with nodal metastasis who underwent POCRT had significantly higher 10-year OS (46.2% vs. 18.2%, P = 0.009) and PFS (38.7% vs. 10.0%, P = 0.009) rates than those treated with PORT alone. The presence of postoperative macroscopic residual tumor (R2 resection) was identified as an independent prognosticator for inferior OS (P = 0.032), PFS (P = 0.001), and LRC (P = 0.007). Importantly, POCRT significantly correlated with higher 10-year LRC rates in patients with R2 resection (74.2% vs. 40.7%, P = 0.034) or adenoid cystic carcinoma (AdCC, 97.6% vs. 83.6%, P = 0.039). On multivariate analyses, the use of POCRT significantly predicted superior OS (P = 0.037) and PFS (P = 0.013) for node-positive patients and LRC for patients with R2 resection (P = 0.041) or AdCC (P = 0.005). ConclusionsFor surgically resected SGC, POCRT was associated with improved long-term OS and PFS for patients with nodal metastasis and superior LRC for patients with R2 resection or AdCC.

The Benefits of Adjuvant Trastuzumab for HER-2-Positive Salivary Gland Cancers.

Although high-grade salivary gland cancers (SGCs) often express androgen receptor (AR) and/or HER-2/neu, therapeutically targeting these receptors in SGC remains investigational. We investigated the prevalence of receptor expression and the benefit of adjuvant HER-2 directed therapy in the high-risk postoperative setting and explored the clinical utility of sequentially targeting these receptors in the setting of advanced disease. We clinically annotated 95 patients with SGC (excluding adenoid cystic carcinoma) treated at our institution from 2002 to 2019 and recorded AR, HER-2/neu status, and tumor genomic profiling results when available. Clinicopathologic information was then integrated with outcomes. Of 95 patients, most had high-risk histologies, with salivary duct carcinoma (SDC) as the most frequent diagnosis (43, 45%). Thirty-five (37%) experienced recurrence (51% SDC). HER-2/neu was positive (1-3+) by immunostaining in 34 of 52 (65%) evaluable cases. There was no difference in survival based on HER-2/neu or AR expression. Nine of 17 (53%) patients with HER-2+ SDC received adjuvant chemoradiation with trastuzumab. Median disease-free survival (DFS) and overall survival (OS) were longer among patients with HER-2/neu 3+ staining tumors who received adjuvant trastuzumab versus those who did not (DFS, 117 vs. 9 months; p = .02; OS, 74 vs. 43 months; p = .02), with no difference among other HER-2/neu subgroups (0-2+). Two of nine (22%) patients treated with adjuvant trastuzumab demonstrated recurrence, both with low HER-2/neu staining intensity (1+). Longer time to recurrence (hazard ratio, 0.94; p = .01) predicted improved outcomes. Both androgen deprivation and HER-2-directed therapies had clinical benefit beyond the first-line metastatic setting, with partial response observed beyond second-line use. Although prospective data are lacking, the use of adjuvant trastuzumab in high-risk patients with SGC appears beneficial, particularly among patients with tumors exhibiting HER-2/neu 3+ immunostaining. Results of this study showed an improved disease-free and overall survival in patients treated with adjuvant trastuzumab for high-risk salivary gland cancers with strong HER-2/neu staining intensity. Following recurrence or metastatic spread, sequential HER-2, and androgen-directed therapies may benefit certain patients with salivary gland cancer.

Adjuvant Radiation and Chemoradiation for High-Risk Salivary Gland Malignancies: A 20-Year Single Institution Experience

To report our institutional outcomes of patients with non-previously treated, high-risk salivary gland malignancies treated with surgery followed by adjuvant radiation (RT) and chemoradiation (CRT). From January 1997 to December 2017, 108 patients were treated with surgery, and adjuvant RT (n = 50) or CRT (n = 58) for high-risk pathologic features: perineural involvement (PNI), lymphovascular space invasion (LVSI), positive/close (<2mm) margin, high grade, extracapsular extension (ECE), or positive lymph nodes. Adjuvant RT was delivered in 2 Gy daily fractions, and adjuvant CRT was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m2 on d1), infusional 5-fluorouracil (600 mg/m2/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment. The Kaplan-Meier method was used to estimate rates of locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). Regression analyses were used to identify factors associated with LRC, DFS, and OS. Multivariable Cox Regression (MVA) was performed for known confounding risk factors, and factors associated with a trend to significance (p <0.20). Chi-Square was used to compare rates of toxicities between groups. Median follow-up was 52 months (range: 3 - 226). The most common histologies included: Adenoid Cystic (n = 30), Mucoepidermoid (n = 20), and Salivary Duct Adenocarcinoma (n = 18). The most common location included the parotid (n = 73). The median RT dose was 66 Gy (range 43.2 - 74 Gy). The 5-year LRC was 88%, 5-year DFS was 57%, and 5-year OS was 78%. On MVA, LRC was not associated with any factors; DFS was associated with the size of the tumor (HR 2.0, p = 0.01), tumor location (HR 2.0, p = 0.01), and stage (HR 1.7, p = 0.02); and OS was associated with N stage (HR 2.3, p = 0.005), LVSI (HR 1.9, p = 0.012), ECE (HR 1.5, p = 0.032), and stage (HR 1.3, p = 0.05). CRT was not associated with improved LRC (HR 0.5, p = 0.34), DFS (HR 0.4, p = 0.44), or OS (HR: 0.46, p = 0.384). Since 87% of node positive patients were treated with adjuvant CRT compared to 13% with RT, therefore comparison was not possible. There was no difference in any acute or late grade 3+ toxicities, or parenteral nutrition between RT and CRT (p = 0.98, p = 0.85, and p = 0.83), respectively. There was one acute grade 5 toxicity in the RT group. To our knowledge, this is the largest single institution cohort of adjuvant CRT for high-risk salivary malignancies. Overall, adjuvant CRT doesn’t enhance outcomes compared to adjuvant RT alone. However, LRC was similar between RT and CRT groups in spite of more adverse features (nodal disease and ECE) in the CRT group. Distant metastatic disease remains a significant pattern of failure. We await large prospective evidence to determine which subsets of patients benefit from adjuvant CRT.

Adjuvant Radiation Therapy (RT) With or Without Chemotherapy in Resected High-Risk Salivary Gland Malignancies (SGM): A National Cancer Data Base (NCDB) Analysis

Adjuvant Radiation Therapy (RT) With or Without Chemotherapy in Resected High-Risk Salivary Gland Malignancies (SGM): A National Cancer Data Base (NCDB) Analysis

Proton versus conventional radiotherapy for pediatric salivary gland tumors: Acute toxicity and dosimetric characteristics.

10040 Background: Adjuvant radiotherapy (RT) is often a component of treatment for high-risk salivary gland tumors. Minimizing irradiation of surrounding normal tissues is particularly important fo...

IMRT with Stereotactic Body Radiotherapy Boost for High Risk Malignant Salivary Gland Malignancies: A Case Series.

Patients with high risk salivary gland malignancies are at increased risk of local failure. We present our institutional experience with dose escalation using hypofractionated stereotactic body radiotherapy (SBRT) in a subset of this rare disease. Over the course of 9 years, 10 patients presenting with skull base invasion, gross disease with one or more adverse features, or those treated with adjuvant radiation with three or more pathologic features were treated with intensity-modulated radiation therapy followed by hypofractionated SBRT boost. Patients presented with variable tumor histologies, and in all but one, the tumors were classified as poorly differentiated high grade. Four patients had gross disease, three had gross residual disease, three had skull base invasion, and two patients had rapidly recurrent disease (≤6 months) that had been previously treated with surgical resection. The median stereotactic radiosurgery boost dose was 17.5 Gy (range 10–30 Gy) given in a median of five fractions (range 3–6 fractions) for a total median cumulative dose of 81.2 Gy (range 73.2–95.6 Gy). The majority of the patients received platinum based concurrent chemotherapy with their radiation. At a median follow-up of 32 months (range 12–120) for all patients and 43 months for surviving patients (range 12–120), actuarial 3-year locoregional control, distant control, progression-free survival, and overall survival were 88, 81, 68, and 79%, respectively. Only one patient failed locally and two failed distantly. Serious late toxicity included graft ulceration in one patient and osteoradionecrosis in another patient, both of which underwent surgical reconstruction. Six patients developed fibrosis. In a subset of patients with salivary gland malignancies with skull base invasion, gross disease, or those treated adjuvantly with three or more adverse pathologic features, hypofractionated SBRT boost to intensity-modulated radiotherapy yields good local control rates and acceptable toxicity.

Postoperative Chemoradiation Therapy in High-Risk Salivary Gland Cancers

High risk salivary cancers are ordinarily treated with surgery and postoperative radiation therapy (PORT). Concurrent chemotherapy with PORT (CRT) has been shown to intensify treatment and improve outcomes in squamous carcinomas of the head and neck. We sought to retrospectively compare outcomes of PORT and CRT in salivary gland carcinomas.

Long‐term outcomes of surgery followed by radiation therapy for minor salivary gland carcinomas

Postoperative radiation therapy is often used in patients with high-risk salivary gland carcinomas. In this study we evaluated the outcomes and prognostic factors in patients with minor salivary gland cancers treated with adjuvant radiation therapy. Retrospective cohort study. We performed a retrospective analysis of 90 patients treated with curative intent. Median follow-up was 71 months. Fifty-eight patients (64%) had adenoid cystic carcinomas, 22 (24%) had adenocarcinomas, and 10 (11%) had mucoepidermoid cancers. Primary disease site included 39 (43%) sinonasal, 35 (39%) oral cavity, 10 (11%) oropharynx, and six (7%) others. Twenty-seven patients (30%) were treated with intensity-modulated radiation therapy. Eight local, four neck, and 24 distant relapses were detected. Local control rates at 5 and 10 years were 90% and 88%, respectively. Advanced T stage was associated with worse local control. Distant metastasis rates were 24% and 28% at 5 and 10 years, respectively. Tumor stage, histology, perineural invasion, and lymphovascular space invasion were significant predictors of distant metastasis on univariate analysis. However, on multivariate analysis only the American Joint Committee on Cancer stage was significant. Overall survival rates were 76% and 63% at 5 and 10 years, respectively. More advanced T stage and N stage correlated with worse overall survival. Tumor stage remains the best predictor for locoregional and distant disease control of minor salivary gland cancers. Postoperative radiation therapy for high-risk patients results in excellent long-term locoregional disease control. Further work is needed to improve systemic control.

Management of salivary gland tumors

Surgery after proper imaging (MRI or CT scan) is the main stay of treatment for salivary gland tumors. Although excision margins should be ≥5 mm for malignant tumors in cases of parotid gland carcinoma, the facial nerve should be preserved whenever it is not infiltrated. Adjuvant external radiation is indicated for malignant tumors with high-risk features such as close (or invaded) margins, perineural speed, lymphatic and/or vascular invasion, lymph-node involvement and high-grade histology. A Phase II trial testing adjuvant concomitant cisplatin plus radiation therapy versus adjuvant radiation therapy alone after surgery is currently under investigation for high-risk salivary gland cancer. For inoperable cancers, photons combined with proton boost seem to be a valuable option. Even if protons or carbon ions are promising, access to the latter is limited for usual treatment. For recurrent and/or metastatic cancer, polychemotherapy (cisplatin based) gives a 25% response rate in adenoid cystic carcinoma and should be used when the disease is overtly in progression. Targeted therapies with anti-EGF receptor molecules, antiangiogenic agents and tyrosine kinase inhibitors are ongoing, but more trials are needed to establish their efficacy, as is the use of bortezomib followed by doxorubicin. The products of fusion oncogenes, which have a pathogenic role in some adenoid cystic carcinoma and mucoepidermoid carcinomas, are of interest as potential therapeutic targets.

Concurrent chemoradiotherapy for locoregionally advanced salivary gland malignancies

Locoregionally advanced salivary gland malignancies have a poor prognosis despite aggressive therapy. Herein we report our experience in treating high-risk salivary gland malignancies with concurrent chemoradiotherapy (CRT). Medical records of 15 patients with salivary gland malignancies treated with CRT at our institution between 1997 and 2010 were analyzed. All patients had high-risk characteristics: 80% were stage IV, 54% were ≥ N2, and 47% were unresectable and were treated with definitive CRT. At 2 years, overall survival (OS) was 67%, disease-free survival (DFS) was 44%, and local control was 76%. There were no treatment-related deaths, and patients experienced expected acute side effects. CRT for salivary gland malignancies has acceptable toxicity, CRT is proven beneficial for many other cancers, and some salivary gland malignancies are clinically responsive to chemotherapy. CRT, therefore, should be considered for treatment of high-risk salivary gland malignancies.

Adjuvant chemoradiotherapy for locoregionally advanced and high-risk salivary gland malignancies

BackgroundTo report the outcomes of patients with locoregionally advanced and high- risk salivary gland malignancies treated with surgery followed by adjuvant chemoradiotherapy.MethodsFrom 09/1991 - 06/2007, 24 high-risk salivary gland cancer patients were treated with surgery, followed by adjuvant chemoradiotherapy for high-risk pathologic features including, perineural involvement, nodal involvement, positive margins, or T3/T4 tumors. Chemoradiotherapy was delivered for 4-6 alternating week cycles: the most common regimen, TFHX, consisted of 5 days paclitaxel (100 mg/m2 on d1), infusional 5-fluorouracil (600 mg/m2/d × 5d), hydroxyurea (500 mg PO BID), and 1.5 Gy twice daily irradiation followed by a 9-day break without treatment.ResultsMedian follow-up was 42 months. The parotid gland was more frequently involved (n = 17) than minor (n = 4) or submandibular (n = 3) glands. The median radiation dose was 65 Gy (range 55-68 Gy). Acute treatment related toxicity included 46% grade 3 mucositis and 33% grade 3 hematologic toxicity. Six patients required feeding tubes during treatment. One patient progressed locally, 8 patients progressed distantly, and none progressed regionally. Five-year locoregional progression free survival was 96%. The 3 and 5 year overall survival was 79% and 59%, respectively. Long-term complications included persistent xerostomia (n = 5), esophageal stricture requiring dilatation (n = 1), and tempromandibular joint syndrome (n = 1).ConclusionsSurgical resection followed by adjuvant chemoradiotherapy results in promising locoregional control for high-risk salivary malignancy patients.

Outcomes of Postoperative Concurrent Chemoradiotherapy for Locally Advanced Major Salivary Gland Carcinoma

To investigate the potential value of postoperative concurrent chemoradiation among patients with high-risk salivary gland carcinomas. Case control study based on retrospective medical record review. A tertiary care comprehensive cancer center. A total of 24 patients, 12 with major salivary gland carcinoma who were treated with postoperative concurrent chemoradiotherapy from 1998 to 2007 (chemoradiation group), and a control group of 12 patients treated with postoperative radiation alone. Overall survival, progression-free survival, toxic effects. All but 1 patient had stage III or IV disease; close or positive surgical margins were identified in 20 patients (83%). The median radiation dose was 63 Gy. In the chemoradiation group, platinum-based regimens were used in all. Treatment was well tolerated, but toxic effects, predominantly hematologic, were increased in the chemoradiation group. To date, 8 patients have died; the median overall survival was 53 months. The overall survival in the chemoradiation group was significantly better than in the radiation-alone group: 3-year survival rates were 83% and 44%, respectively (P = .05). Locally advanced or high-grade salivary gland carcinomas follow an aggressive clinical course. Based on our limited experience, postoperative chemoradiation with a platinum-based regimen seems to be effective in selected patients and warrants further investigation.

Pilot study of paclitaxel and carboplatin (P/C) with concurrent radiation therapy (RT) in high risk salivary gland carcinomas (SGC)

15538 Background: Standard therapy for high risk SGC includes surgical resection with adjuvant RT, but a high risk of recurrence exists. The role of chemotherapy in this setting has not been fully defined. Methods: This limited institution pilot study evaluated the use of P/C with concurrent RT as adjuvant treatment of high risk SGC. The primary objective was to assess toxicity of this treatment in anticipation of a larger cooperative group phase II study. Eligible patients (pts.) had a Southwest Oncology Group (SWOG) performance status (PS) of 0–2 who after surgical resection of their SGC had high risk features including positive surgical margins, perineural invasion, multiple lymph node (LN) metastases, or extracapsular extension. Treatment included P = 40 mg/m2 intravenously followed by C = AUC of 2 concurrently on days 1, 8, 15, 22, 29, 36 of RT. RT consisted of a total dose of 60 Gy in 30 fractions to the primary and regional LN sites of disease. Results: Five pts. were enrolled 4 with adenoid cystic CA and 1 with high grade mucoepidermoid CA. Median age was 59 years (32–69), all with SWOG PS = 0. Four pts. completed the full 6 cycle P/C chemotherapy; all completed RT per protocol. Grade III/IV mucositis, the most common toxicity, occurred in 6 of 30 (20%) P/C cycles, leading to alteration of therapy in 1 pt. There was no reported neuropathy or significant laboratory abnormalities. Median follow up was 17.5 months (mos.); most were disease free at last follow up (13 to 37 mos.); 1 recurred at 14 mos.; this pt. accounts for the only death observed. One year survival was 100%. Conclusions: The regimen of P/C with concurrent RT, as defined, was tolerated well. Grade III/IV mucositis was the main toxicity. Based on the overall tolerability of this regimen, we believe that this postoperative combined modality therapy deserves further study in a larger cooperative group phase II trial to further define its toxicity and efficacy in high risk SGC. We thank Bristol Myers Squibb for support of this study. No significant financial relationships to disclose.