Treatment Of Salivary Gland Cancer Research Articles

Current management and future challenges in salivary glands cancer.

Salivary gland cancers (SGCs) are rare, accounting for less than 5% of all malignancies of the head and neck region, and are morphologically heterogeneous. The diagnosis is mainly based on histology, with the complementary aid of molecular profiling, which is helpful in recognizing some poorly differentiated, borderline, or atypical lesions. Instrumental imaging defines the diagnosis, representing a remarkable tool in the treatment plan. Ultrasound and magnetic resonance are the most common procedures used to describe the primary tumour. The treatment of SGCs is multimodal and consists of surgery, radiotherapy, and systemic therapy; each treatment plan is, however, featured on the patient and disease's characteristics. On 24 June 2022, in the meeting "Current management and future challenges in salivary gland cancers" many experts in this field discussed the state of the art of SGCs research, the future challenges and developments. After the meeting, the same pool of experts maintained close contact to keep these data further updated in the conference proceedings presented here. This review collects the insights and suggestions that emerged from the discussion during and after the meeting per se.

Posttherapeutic quality of life after treatment of salivary gland cancer

In addition to overall survival and recurrence-free interval, posttherapeutic quality of life has been established as an independent criterion for treatment evaluation. Thereby, both the specific changes in the head and neck region and their objectification represent aparticular challenge for the assessment of quality of life. There are different validated questionnaires available. Based on the literature, an overview of the relevant questionnaire instruments is given and the specific aspects in patients with salivary gland cancer are presented. Aselective literature search was conducted to collect publications dealing with the assessment of health-related quality of life in head and neck tumor patients. The papers were critically appraised and summarized. There are some validated questionnaires available to measure quality of life in patients with head and neck tumors as well as afew specific questionnaires for patients after parotidectomy. By assessing quality of life using standardized questionnaire instruments, disease and treatment consequences can be objectified. Thus, the need for supportive measures, e.g., for rehabilitation in facial nerve palsy, can be identified more reliably.

Proton Therapy for Major Salivary Gland Cancer: Clinical Outcomes.

PurposeTo report clinical outcomes in terms of disease control and toxicity in patients with major salivary gland cancers (SGCs) treated with proton beam therapy.Materials and MethodsClinical and dosimetric characteristics of patients with SGCs treated from August 2011 to February 2020 on an observational, prospective, single-institution protocol were abstracted. Local control and overall survival were calculated by the Kaplan-Meier method. During radiation, weekly assessments of toxicity were obtained, and for patients with ≥ 90 days of follow-up, late toxicity was assessed.ResultsSeventy-two patients were identified. Median age was 54 years (range, 23-87 years). Sixty-three patients (88%) received postoperative therapy, and nine patients (12%) were treated definitively. Twenty-six patients (36%) received concurrent chemotherapy. Nine patients (12%) had received prior radiation. All (99%) but one patient received unilateral treatment with a median dose of 64 GyRBE (relative biological effectiveness) (interquartile range [IQR], 60-66), and 53 patients (74%) received intensity-modulated proton therapy with either single-field or multifield optimization. The median follow-up time was 30 months. Two-year local control and overall survival rates were 96% (95% confidence interval [CI] 85%-99%) and 89% (95% CI 76%-95%], respectively. Radiation dermatitis was the predominant grade-3 toxicity (seen in 21% [n = 15] of the patients), and grade ≥ 2 mucositis was rare (14%; n = 10 patients). No late-grade ≥ 3 toxicities were reported.ConclusionProton beam therapy for treatment of major SGCs manifests in low rates of acute mucosal toxicity. In addition, the current data suggest a high rate of local control and minimal late toxicity.

Orphan designation: Larotrectinib, Treatment of salivary gland cancer

Orphan designation: Larotrectinib, Treatment of salivary gland cancer

1169P - Development and characterization of salivary gland cancer organoid cultures

BackgroundRecently 3D organoid cell cultures have been established for a variety of human cancers. Salivary gland cancer (SGC) is a rare cancer with 22 different subtypes and few treatment options. Our aim is to generate a large repertoire of patient-derived SGC organoids with different phenotypes, which will facilitate pre-clinical and pharmacological studies. MethodsFresh tissues of resected primary tumours and/or metastases of SGC patients were collected. Tissues were minced and digested with collagenase type 2 and TrypLE to generate single cells. After washing, the cells were seeded in growth factor reduced Matrigel. Organoid medium, containing Rho kinase inhibitor Y27632, was refreshed twice a week. Viable organoids were characterized by immunohistochemistry and by DNA/RNA sequencing. Moreover, the organoids were used to evaluate various treatments that are or may be relevant for the treatment of SGC. ResultsBetween 2016 and 2018 we obtained tissue of 17 SGC patients, of which 16 contained sufficient material for processing: 10 salivary duct carcinoma (SDC), 3 adenoid cystic carcinoma (ACC), 2 muco-epidermoid carcinoma (MEC) and 1 parotid adenocarcinoma not otherwise specified (NOS). For 5 tumors (2 SDC, 2 ACC, 1 adenocarcinoma NOS) viable organoids were established, which could be passaged at least three times. Organoids cultures derived from the other tumours stopped growing after the first passage. Viable organoids showed resemblance with the original primary tumour, based on morphology, protein expression, and growth pattern. Various drugs were tested at a single dose, and showed reduced organoid cell growth compared to untreated controls. Moreover, a dose-response relationship was established for an ALK-positive MEC organoid that was treated with crizotinib. Finally, epithelial-mesenchymal transition was shown in SDC organoids of a primary tumour and a lymph node metastasis of the same patient. ConclusionsWe are the first that have successfully developed and characterized long-term organoid cultures for ACC and SDC. These organoid cell lines will facilitate pre-clinical and pharmacological studies. Other SGC organoid cultures do not grow infinitely, but do provide an in vitro model to study different treatments during initial growth. Legal entity responsible for the studyRadboud University Medical Center. FundingDutch Salivary Gland Cancer Patient Platform. DisclosureAll authors have declared no conflicts of interest.

Treatment difficulties in salivary gland cancer

Abstract Salivary gland cancers are represented by a heterogeneous histologic group of tumors, with low incidence, which may appear both in major and minor salivary glands. This article presents a review of the difficulties which may be encountered in this pathology during the treatment. The diagnosis of salivary gland cancers is often delayed, due to the histopathologic and immunohistochemistry results given in different period of times. There can be several difficulties in following the oncologic pre-treatment protocols, in terms of imaging technique, as MRI, useful for disease staging. The treatment of salivary gland cancers is complex, due to the local anatomy and their aggressive potential. Because of their decreased incidence, there are few data that investigate the treatment in the case of these diseases. The current therapy available for the patients with salivary gland cancers is represented by complete surgical resection. Several treatment difficulties in cancers of the salivary glands may come from the surgical limitations and the insufficient data for adjuvant and palliative treatment. Due to the limitations of the local health system, there is a heterogeneous distribution of the oncologic centers, lack of equipment, prolonged time to follow general protocols, despite the aspect of case-individualized therapy according to the guidelines. We must not forget the tumor behaviour and individual reactivity of different patients to the same treatment protocol.

Management of salivary gland carcinomas - a review.

Salivary gland carcinomas are a heterogeneous group of tumors with many histological subtypes which occur in both major and minor salivary glands. However, they have a relatively low of incidence. Their rarity limits study size and the ability to perform phase III trials. Therefore, to date, the entire management is usually varied. Certain published studies have paid more attention to the systemic therapy in the management of metastatic or locally recurrent salivary gland cancer, while little effort has been made to study the entire management for this lesions. Although results of treatment for patients with salivary gland carcinoma have improved in recent years, the treatment of salivary gland cancers is still not standardized. And some patients who haven’t received optimal treatment strategies had a reduced survival. In this review, the topics covered include surgery and radiotherapy, selective neck dissection, chemotherapy, and targeted therapy, which aimed to summarize the optimal management approaches and to develop recommendations for managing this lesions. For these rare cancers, there is also a need for a determined, coordinated effort to conduct high-quality clinical trials.

Convallaria keiskei as a novel therapeutic alternative for salivary gland cancer treatment by targeting myeloid cell leukemia-1.

Various chemotherapeutic agents have been used largely for the treatment of salivary gland cancer. However, results are disappointing, and these agents can cause some serious side effects. Therefore, recent studies have focused on the possible roles of natural products to overcome these limitations. Salivary gland cancer cells treated with or without Convallaria keiskei (MECK) for 24 hours. Apoptotic changes were evaluated by live/dead assay, immunoblotting, and expression levels of caspase-3 and B-cell lymphoma-2 family member. MECK significantly inhibited salivary gland cancer growth. At the molecular level, MECK dramatically reduced myeloid cell leukemia-1 (Mcl-1) in a translation-dependent manner and thereby induced apoptosis through Bax/Bid. Furthermore, we found that Mcl-1 could be a potential therapeutic target of MECK-induced apoptosis and its stability is regulated by extracellular signal-regulated kinases 1/2 (ERK1/2) signaling MECK can be used as a safe and efficient therapeutic alternative for the treatment of salivary gland cancer. © 2015 Wiley Periodicals, Inc. Head Neck 38: E761-E770, 2016.

Advances in diagnosis and treatment of salivary gland cancer

Advances in diagnosis and treatment of salivary gland cancer

Targeting Id1 reduces proliferation and invasion in aggressive human salivary gland cancer cells

BackgroundSalivary gland cancer (SGC) is one of the common malignancies of the head and neck area. It develops in the minor and major salivary glands and sometimes metastasizes to other organs, particularly to the lungs. Inhibitors of differentiation (Id) proteins are negative regulators of basic helix-loop-helix transcription factors that control malignant cell behavior and tumor aggressiveness in many tissues. In this study, our goal was to determine the potential role of Id proteins, particularly Id1, during human SGC cell progression.MethodsWe first determined the expression levels of Id1 and Id2 in four SGC cell lines: two adenocarcinoma of the salivary gland (HSG and HSY) and two adenoid cystic carcinoma (ACC2 and ACCM) cell lines. We then used constructs that expressed antisense cDNAs to Id1 or Id2 to knockdown the expression of these proteins in cell lines where they were highly expressed, and determined the effects of the knockdown on cell proliferation, migration and invasion.ResultsId1 mRNA and protein were detectable in all cell lines, and expression of Id2 was variable, from absent to high. The ACC2 and ACCM cell lines expressed both Id1 and Id2, but Id1 was expressed at a higher level in the more aggressive ACCM cell line in comparison toACC2 cells as confirmed by Id1 promoter-reporter assays. We therefore focused on the ACCM cells for the remainder of the study. We found that proliferation and invasiveness of ACCM cells were strongly reduced after Id1 knockdown whereas Id2 suppression had only a slight effect. Results of scratch and colony formation assays also confirmed that ACCM cell aggressiveness was significantly reduced upon Id1 knockdown. Finally, this knockdown resulted in reduced c-myc and enhanced cyclin-dependent kinase inhibitor p21 expression.ConclusionsThese results demonstrate that Id1 plays an important role in the control of human SGC cell aggressiveness and suggest a potential role as a marker of diagnosis, prognosis and progression of SGCs. Id1 suppression could represent a novel and effective approach for the treatment of salivary gland cancer.

Acinic cell carcinoma of the parotid gland with skull base invasion: Case study, managed by exclusive external 3D radiation therapy

To review treatment options in a rare type of parotid tumor, in a clinical case study. A 62-year-old woman presenting with recurrence of acinic cell carcinoma of the parotid gland with invasion of the skull base was treated by external 3D conformational radiation, having refused large-scale exeresis. Sixty-six Gy (70Gy equivalent) were delivered in 2007. Clinical and paraclinical follow-up found regular tumor volume regression over a 2.5-year period without side-effects of radiation. There are no specific data on the efficacy of external radiation therapy in acinic cell carcinoma; reports on exclusive radiation treatment of salivary gland cancer include different histological types. Exclusive radiation treatment should be at least 66-70Gy, preferably by neutron- or hadrontherapy. Management of acinic cell carcinoma of the parotid is surgical with possible secondary radiation therapy; exclusive external radiation therapy is, however, an option in case of contra-indication for surgery or patient refusal.

Base of skull recurrences after treatment of salivary gland cancer with perineural invasion reduced by postoperative radiotherapy

To determine the effect of postoperative radiation therapy for salivary gland carcinomas in the presence of microscopic perineural invasion. Retrospective review at an academic tertiary center. One hundred and forty patients with pathological evidence of perineural invasion at the time of initial surgery for salivary gland carcinomas were analysed. Sixteen patients (11%) had major (named) nerve involvement. Ninety-four patients (67%) received postoperative radiation therapy to the primary site, and the portal films of 65 of these patients were available for review. The incidence of skull base recurrences among patients treated by surgery with or without postoperative radiation therapy. Ten patients experienced skull base recurrences. T4 disease and the omission of postoperative radiation therapy were identified as significant predictors of skull base recurrence. Postoperative radiation therapy reduced the actuarial probability of skull base recurrence from 15% to 5% (P = 0.03). The crude rates of skull base recurrence were 6% (2/35) and 10% (3/30), respectively, for patients whose skull base were and were not confirmed to be encompassed in the irradiation field. The 5-year overall survival for patients who experienced a skull base recurrence was 19% compared to 91% for those who did not (P < 0.001). The use of postoperative radiation therapy significantly reduced the incidence of skull base recurrence among salivary gland carcinoma patients with perineural invasion.

Basic evidence of molecular targeted therapy for oral cancer and salivary gland cancer

Recently, attention has been focused on molecular targeted cancer therapy in various tumors. Although there is no single consistent molecular target specific for oral squamous cell carcinoma (OSCC) and salivary gland cancer (SGC), there are a number of promising candidate proteins. The aim of this review is to introduce the basic evidences to support the molecular targeting for OSCC and SGC. We focused on the 4 molecules, epidermal growth factor receptor (EGFR), cyclooxygenase-2 (COX-2), peroxisome proliferator-activated receptor gamma (PPARgamma), and progesterone receptor, that are, respectively, associated with the proliferation and the differentiation of OSCC and SGC. Gefitinib ("Iressa," ZD1839), a small molecule EGFR tyrosine kinase inhibitor, can inhibit the proliferation of OSCC cell lines in a dose- and time-dependent manner and lead to cell cycle arrest with accumulation of cells in the G1 phase, and a decrease of cells in S phase. The agent suppressed tumor metastasis in the animal model. Furthermore, a cooperative antiproliferative effect was obtained when cancer cells were treated with radiation followed by gefitinib. While radiation alone did not significantly affect p38 mitogen-activated protein kinase and MAP kinase kinase (MEK)1/2 autophosphorylation, the combination of gefitinib and radiation completely inhibited the downstream signaling of EGFR. Gefitinib enhanced tumor radioresponsiveness by multiple mechanisms, including the growth inhibition and effects on DNA repair after exposure to radiation. Next, the level of COX-2 expression correlated inversely with increased tumor radiation sensitivity. Treatment with celecoxib, a COX-2 selective inhibitor, enhanced the radioresponsiveness of HSC-2 cells, which constitutively expressed COX-2. Another promising molecular target is the PPARgamma, which is a member of the nuclear receptor superfamily of ligand-activated transcription factors. Recent studies have demonstrated that PPARgamma ligands induce cellular differentiation and inhibit cell growth in carcinomas of various types. These data suggest that synthetic PPARgamma ligands may be useful for molecular targeting of oral cancer. Finally, the possibility of using molecular targeted therapy directed at hormone receptors in the treatment of advanced SGCs was described. The basic data strongly suggested the possibility of tumor suppression by targeting these molecules. Studies of different targeted agents alone or with more conventional treatment modalities are needed to fully determine what role the targeted therapy will play in the management of patients with OSCC and SGC.

Salivary gland tumors--tumor typing and grading

In addition to staging, histological typing and grading provide important information for prognosis and adequate treatment of salivary gland cancers. Current classification and grading systems for mucoepidermoid carcinoma, adenoid cystic carcinoma, and malignant mixed tumor (carcinoma ex pleomorphic adenoma) are discussed.

Fast neutron radiation for inoperable and recurrent salivary gland cancers.

The current standard treatment of salivary gland cancers consists of surgical resection, with or without postoperative low linear energy transfer (LET) radiation, resulting in high locoregional control rates. However, tumor control prognosis is poor when conventional radiation is used alone for advanced, inoperable cases. An extensive review of the world's literature on fast neutron irradiation for inoperable, unresectable, or recurrent malignant salivary gland neoplasms is presented and compared with the experience using conventional low LET radiotherapy. The pooled data indicate a locoregional control rate of 67% for fast neutrons versus 25% for photons and/or electrons in the treatment of such advanced disease. The radiobiological rationale supporting this observed increase in tumor control is discussed. The overall significant late complication rate is 19%, but several suboptimal treatment factors were present that contributed substantially to the reported toxicity. With the modern machines and treatment techniques now available, the evidence overwhelmingly supports the role of fast neutron radiation as the treatment of choice for inoperable and recurrent salivary gland cancers.

Chemotherapy for salivary gland cancer.

Because of the scarcity of such lesions, little is known about the efficacy of chemotherapy for advanced salivary gland cancers. Although surgery and irradiation are the mainstays of treatment, patients with recurrent tumors and those with unresectable or metastatic cancer are not candidates for this usual approach. Ten patients with recurrent, metastatic, or unresectable salivary gland tumors were treated with combination chemotherapy, primarily with cisplatin, doxorubicin hydrochloride (Adriamycin), and cyclophosphamide, or cisplatin with 5-fluorouracil. In patients whose tumors exhibited no response, second-line drugs were used. The overall response rate was 50%--with one complete response--but the duration of response was short. This report contributes to the growing data base that demonstrates definite chemosensitivity of these tumors. To date, 116 patients have been reviewed. Adenocarcinoma-like cancers respond best to cisplatin, doxorubicin hydrochloride, and 5-fluorouracil. High-grade mucoepidermoid carcinoma may show a sensitivity similar to that of squamous cell carcinoma. Multi-institutional protocols need to be developed to assess the roles of adjuvant and palliative chemotherapy in the treatment of salivary gland cancer.