Treatment Of Salivary Gland Malignancies Research Articles

Novel therapeutic approaches for salivary gland carcinomas

Novel therapeutic options for the treatment of salivary gland malignancies have emerged due to the improvement and distribution of molecular pathological testing methods and the availability of targeted therapies. Since they are less toxic, these new agents are a valuable alternative to conventional cytotoxic chemotherapy. On the one hand, there are new entity-specific therapies such as NTRK inhibitor therapy for secretory carcinomas and axitinib therapy for adenoid cystic carcinomas. Moreover, cross-entity therapeutics such as antiandrogenic therapy, HER2 inhibition, and PI3K inhibition are also coming to the fore. For metastatic/recurrent salivary gland carcinomas that cannot be treated with targeted therapy, platinum-based chemotherapies continue to be therapy of choice.

Preservation, reconstruction, and rehabilitation of the facial nerve

Der Umgang mit dem N. facialis ist bei der Operation eines Parotiskarzinoms wichtig für die Langzeitlebensqualität des Patienten. In etwa 2 Drittel der Fälle ist der N. facialis nicht vom Tumor befallen. In diesen Fällen sind neben vollständiger Tumorentfernung die Identifizierung und der Erhalt des Nervs für eine erfolgreiche Operation wesentlich. Ist der Nerv vom Tumor infiltriert, muss der betroffene Teil des Nervs im Rahmen einer radikalen Parotidektomie reseziert werden. Die primäre Nervenrekonstruktion, sofern möglich, führt zu den besten funktionellen und kosmetischen Langzeitergebnissen. Das individuell optimale Therapiekonzept basiert zum einen auf der klinischen Prüfung der Gesichtsbeweglichkeit, zum anderen auf der präoperativen Bildgebung, um die Lagebeziehung zwischen Tumor und Nerv zu verstehen, und schließlich auf einer elektrophysiologischen Untersuchung zur Funktion des Nervs. Intraoperativ hilft ein standardisiertes Vorgehen, um den Nerv zu identifizieren und zu erhalten. Wenn eine radikale Parotidektomie indiziert ist, kann bereits die präoperative Diagnostik helfen, neben der einzeitigen Rekonstruktion auch die adjuvante postoperative Therapie zu planen. Das Ziel der Rehabilitation ist die Wiederherstellung von Tonus, Symmetrie und Bewegung des gelähmten Gesichts. Die Wiederherstellung des Augenschlusses hat hohe Priorität. Bei der chirurgischen Therapie von Gesichtslähmungen gab es in den letzten Jahren viele Verbesserungen. Die vorliegende Arbeit gibt einen Überblick über die jüngsten Fortschritte in der Diagnostik, den Operationstechniken und weiteren Möglichkeiten zur Protektion des gesunden N. facialis. Anderseits wird die Rehabilitation des tumorinfiltrierten N. facialis im Kontext der Behandlung von Speicheldrüsenmalignomen beschrieben.

Concurrent Chemoradiotherapy in the Adjuvant Treatment of High-risk Primary Salivary Gland Malignancies.

Adjuvant radiation therapy (RT) is indicated for patients with salivary gland malignancies with risk factors for recurrence following resection. We analyzed patients treated with adjuvant RT with or without concurrent chemotherapy to determine the impact of prognostic and treatment factors. Retrospective analysis was performed of 128 patients treated with surgical resection followed by intensity-modulated radiotherapy. In total, 31 (24.2%) patients were treated with concurrent chemoradiotherapy. The Kaplan-Meier method was used to estimate rates of progression-free survival (PFS), local-regional control, distant control, overall survival. Multivariable Cox regression was performed to evaluate factors significant on univariate analysis. The 5-year rates of PFS, local-regional control, freedom-from distant metastasis, and overall survival were 61.2%, 85.8%, 76.5%, and 73.7%, respectively. Predictors of decreased PFS on univariate analyses were age, tumor stage, nodal stage, positive surgical margins, histology, high grade, perineural invasion, lymphovascular space invasion, extranodal extension, and use of chemoradiotherapy. On multivariable analysis, elevated T-stage, positive surgical margins, and presence of extranodal extension were predictive of decreased PFS. The acute toxicity rates were 30.3% grade 1, 51.5% grade 2, 11.4% grade 3, and 0.8% grade 4. There was no difference in rates of grade 3 or higher acute toxicity with use of RT alone versus chemoradiotherapy (P=0.183). Use of chemoradiotherapy for adjuvant treatment of salivary gland malignancies was well-tolerated, but no improvement in survival was seen with the use of chemoradiotherapy in both the overall study population and a subset with high-risk features. Caution should be used when using this modality until randomized evidence becomes available.

Surgery for Primary Malignant Parotid Neoplasms.

The successful treatment of salivary gland malignancies originating in the parotid gland begins with rigorous and thorough surgical management coupled with the directed and appropriate potential adjuvant use of radiation therapy and chemotherapy. The anatomic complexity of the region in relation to the facial nerve and adjoining neurovascular and musculoskeletal structures requires sound surgical planning and decision making based on preoperative and intraoperative findings. The clinical presentation of parotid malignancy is summarized, as well as the further evaluations that are performed, including imaging and tissue biopsy. A systematic approach to ensure resection with clear margins, management of the facial nerve, applicable extensions of the primary resection and management of the neck are presented. The key determinants of disease control, including the stage (early or advanced), histologic grade (low or high) and margin status (clear or positive), are highlighted as critical aspects of surgical management.

Salivary Gland Tumors Treated With Adjuvant Intensity-Modulated Radiotherapy With or Without Concurrent Chemotherapy

To analyze the recent single-institution experience of patients with salivary gland tumors who had undergone adjuvant intensity-modulated radiotherapy (IMRT), with or without concurrent chemotherapy. We performed a retrospective analysis of 35 salivary gland carcinoma patients treated primarily at the Dana-Farber Cancer Institute between 2005 and 2010 with surgery and adjuvant IMRT. The primary endpoints were local control, progression-free survival, and overall survival. The secondary endpoints were acute and chronic toxicity. The median follow-up was 2.3 years (interquartile range, 1.2-2.8) among the surviving patients. The histologic types included adenoid cystic carcinoma in 15 (43%), mucoepidermoid carcinoma in 6 (17%), adenocarcinoma in 3 (9%), acinic cell carcinoma in 3 (9%), and other in 8 (23%). The primary sites were the parotid gland in 17 (49%), submandibular glands in 6 (17%), tongue in 4 (11%), palate in 4 (11%), and other in 4 (11%). The median radiation dose was 66 Gy, and 22 patients (63%) received CRT. The most common chemotherapy regimen was carboplatin and paclitaxel (n = 14, 64%). A trend was seen for patients undergoing CRT to have more adverse prognostic factors, including Stage T3-T4 disease (CRT, n = 12, 55% vs. n = 4, 31%, p = .29), nodal positivity (CRT, n = 8, 36% vs. n = 1, 8%, p = .10), and positive margins (n = 13, 59% vs. n = 5, 38%, p = .30). One patient who had undergone CRT developed an in-field recurrence, resulting in an overall actuarial 3-year local control rate of 92%. Five patients (14%) developed distant metastases (1 who had undergone IMRT only and 4 who had undergone CRT). Acute Grade 3 mucositis, esophagitis, and dermatitis occurred in 8%, 8%, and 8% (1 each) of IMRT patients and in 18%, 5%, and 14% (4, 1, and 3 patients) of the CRT group, respectively. No acute Grade 4 toxicity occurred. The most common late toxicity was Grade 1 xerostomia (n = 8, 23%). Treatment of salivary gland malignancies with postoperative IMRT was well tolerated with a high rate of local control. Chemoradiotherapy resulted in excellent local control in a subgroup of patients with adverse prognostic factors and might be warranted in select patients.

Surgery and Radiotherapy in the Treatment of Malignant Parotid Tumors: A Retrospective Multicenter Study

Major salivary gland cancers are rare, with many histologic types and subtypes. The low incidence and heterogeneity of primary parotid carcinomas makes their outcome difficult to evaluate. Treatment remains primarily surgical, but optimal therapeutic regimens have yet to be fully realized. The present study reviews the experience of three Italian institutions in the treatment of primary parotid carcinomas in order to describe the clinicopathological presentation and treatment options with emphasis on radiotherapy and to analyze the factors influencing survival. The records of 110 patients with primary parotid neoplastic lesions treated at three Italian institutions from 1993 to 2004 were retrospectively reviewed. Six patients were excluded from the study: 3 received surgery alone and 3 were not assessable, for a total of 104 assessable patients. Acute and late toxicity of radiotherapy was quantified following the recommendations of the RTOG/EORTC. Survival was analyzed by the actuarial Kaplan-Meier product-limit method. The influence of selected factors on 10-year disease-specific survival was analyzed. The 104 assessable patients were treated as follows: 11 patients received radiotherapy as their only treatment (3 with a palliative purpose) and 93 had postoperative radiotherapy. Thirty-two patients underwent neck dissection: neck lymph node metastases were found in all them. Their mean age was 60 years (range, 14-92). According to the UICC/2002 TNM Classification, 8 patients were stage I, 19 stage II, 34 stage III, 25 stage IVA, 5 stage IVB, 3 recurrent and 10 not assessable (Tx). The most frequent histologies were adenoid cystic carcinoma (n = 16), mucoepidermoid carcinoma (n = 15), and acinic cell carcinoma (n = 15). Twenty-three patients had recurrences: 10 had local recurrences, 3 neck recurrences, 9 distant metastases, and 1 patient had both local recurrence and distant metastases. No factors were observed that would negatively influence the prognosis. Actuarial 10-year disease-specific survival was 71% and actuarial 10-year local control 82%. The treatment of salivary gland malignancies remains primarily surgical. Our study confirms the results of the literature with surgery and adjunctive radiotherapy in patients with advanced-stage disease. No variables were observed to influence the prognosis.

Malignant Salivary Gland Tumors-Ten Years Clinicopathological Experience at VGH-Taipei

Malignant salivary gland tumors are uncommon and demonstrate wide diversity of histopathological types and biological behaviors. We report the experience in the management of patients with malignant salivary gland tumors and review the outcome of treatment in an effort to identify significant factors of survival, local recurrence and distant metastases. The age (p=0.002), stage (p＜0.001), histological grade (p=0.020), resection margin (p=0.036) and the presence of neck metastases, local recurrences and distant metastases (p＜0.001) were significantly associated with poorer survival. Local recurrences was correlated with stage (p＜0.001), histology grade (p=0.042), and resection margin (p=0.026). Distant metastases depended on stage (p=0.006), especially tumor size, and facial palsy (p=0.030). The treatment of salivary gland malignancies remains primarily surgical. However, the benefits of combined modality therapy with regard to overall survival await prospective clinical trials.

Management and Outcome of Patients With Malignant Salivary Gland Tumors

Refined imaging technology, the use of external beam radiation, neutron beam therapy, and chemotherapy, has altered management strategies for patients with salivary gland malignancies during the past 2 decades. Although treatment remains primarily surgical, optimal therapeutic regimens have yet to be fully realized. The purpose of this investigation is to report our experience with the management of patients with a variety of malignant salivary gland neoplasms that were treated with various combinations of surgery, radiation, and chemotherapy and to review treatment outcome in an effort to identify predictors of survival and locoregional control. The records of all patients with malignant salivary gland tumors presenting for treatment at our institution between 1992 and 2002 were retrospectively reviewed. Variables were collected and outcome measures were defined in terms of overall survival, disease-free survival, and locoregional control. Descriptive statistics were compiled and statistically evaluated. Survival was described using the Kaplan-Meier method. Prognostic factors were assessed using the Cox proportional hazards model. Clinical and reconstructive factors were reviewed. Eighty-five patients (35 males and 50 females) ranging in age from 16 to 89 years (mean, 58.6 years) met the criteria for inclusion in the study. The majority of tumors were located in the parotid gland (n = 42), with a significant minority located in the minor salivary glands (n = 29), followed by the submandibular gland (n = 8) and the sublingual gland (n = 6). Mucoepidermoid carcinoma was the most common neoplasm (n = 40). More than half of the patients presented in early-stage disease (stage I = 36, stage II = 17, stage III = 8, stage IV = 25). All patients were treated with surgery as the primary modality. Neck dissection was performed in 29% of patients, and more than half (56%) were treated with adjuvant external beam radiation therapy to a dose of 50 to 70 Gy. Patients were, in general, immediately reconstructed at the time of ablation using composite free tissue transfer when appropriate, local/regional rotational flaps, or maxillary obturators. The disease-free survival rate and locoregional control rate at 5 years were 77% and 86%, respectively. Stage (P = .0017), grade (P = .00044), cervical lymph node metastasis (P = .03), and age (P = .01) proved to make a statistically significant contribution when describing outcome. Neither site (P = .5), the presence of positive margins (P = .3), nor perineural invasion (P = .7) had a significant impact on survival. The treatment of salivary gland malignancies remains primarily surgical, although adjunctive radiotherapy may play an important role in those patients with advanced-stage disease. This study confirms the contributions of stage, grade, age, and cervical metastasis for describing survival. The benefits of combined modality therapy awaits prospective clinical trials.

Symposium: Adjuvant cancer therapy of head and neck tumors. The use of postoperative irradiation — its goals and 1978 attainments

AbstractThe use of postoperative irradiation as an adjunctive measure for better control of local and regional disease after a surgical procedure has been used at the Anderson Hospital since approximately 1965. The common clinical setting occurs in those patients in whom, after surgical ablation of the tumor, there are microscopic foci of residual disease at the margins, perineural invasion, histologically a very poorly differentiated carcinoma, dermal lymphatic involvement, multiple nodes in the neck or very large nodes in which the tumor has broken through the nodal capsule and entered the connective tissue. We have been applying this criterion for the treatment of salivary gland malignancies, squamous carcinomas of the hypopharynx and supraglottic larynx, and all sites in the head and neck in which there was extensive cervical nodal metastasis. The results of this therapeutic approach will be reported and discussed.