First experiences with 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancer

Background Advanced salivary gland cancers become difficult to treat when they are technically irresectable and radiotherapy limits are exceeded. There is also an unmet need to improve palliative systemic therapy. Salivary glands depict the Prostate-Specific Membrane Antigen (PSMA) on 68Ga-PSMA-PET/CT, a transmembrane protein that is targeted for diagnosis and treatment of advanced prostate cancer. Some salivary gland carcinomas also express PSMA. Methods This study aimed to retrospectively evaluate the effectiveness of 177Lu-PSMA-617 therapy for recurrent or metastatic salivary gland cancers, as a last resort treatment. Patients with serious tumour-related discomfort for whom no regular option was available were selected and critically re-assessed by the tumour board. Radionuclide therapy eligibility was confirmed when tumour targeting was greater than liver SUVmax on 68Ga-PSMA-PET/CT. The protocol aimed at four cycles of 6.0–7.4 GBq 177Lu-PSMA-617 every 6–8 weeks. Clinical response was evaluated by questionnaires and radiological response by 68Ga-PSMA-PET/CT. Results Six patients were treated with 177Lu-PSMA: four adenoid cystic carcinomas, one adenocarcinoma NOS and one acinic cell carcinoma. In two patients, radiological response was observed, showing either stable disease or a partial response, and four patients reported immediate relief of tumour-related symptoms. Most reported side effects were grade 1–2 fatigue, nausea, bone pain and xerostomia. Four patients prematurely discontinued therapy: three due to disease progression and one due to demotivating (grade 1) side-effects. Conclusions Palliative 177Lu-PSMA therapy for salivary gland cancer may lead to rapid relief of tumour-associated discomfort and may even induce disease stabilization. It is safe, relatively well tolerated and can be considered when regular treatment options fail.

Novel Preclinical Human Salivary Gland Cancer Models Established Using Organoid Culture And Patient-Derived Xenografting

Salivary gland carcinoma (SGC) has poor prognosis depending on the histological subtype. However, due to the scarcity of preclinical experimental models, its pathogenesis remains largely unknown, hampering the development of new treatment modalities for patients with these malignancies. Here, we first report the establishment of a large collection of human SGC experimental models for multiple histological subtypes using patient-derived xenograft (PDX) and organoid culture techniques with our previously optimized method. Additionally, we successfully generated organoids by culturing established PDXs (PDX-derived organoids). Through passaging, each pre-clinical model was confirmed to maintain the pathological characteristics of the original tumor and the genetic traits of corresponding histological subtypes. Finally, we confirmed that these organoids were available for pharmacologic studies. Thus, our comprehensive models of SGC could be a powerful resource for the development of novel therapeutic agents and investigating the pathogenesis of these malignancies.

Radiotherapy in Inoperable Mucoepidermoid Parotid Cancer: A Case Report

Introduction: Salivary gland cancer is an uncommon malignancy in the head and neck. The most common histopathologic type in salivary gland malignancies is mucoepidermoid carcinoma (MEC). Radiotherapy has a role in salivary gland malignancy, especially in inoperable cases and postoperative settings. Definitive or postoperative radiotherapy with or without chemotherapy can improve locoregional control (LRC) in patients with parotid mucoepidermoid carcinoma. Case Presentation: We report a case of a 77-year-old male with inoperable MEC of the right parotid, who received definitive radiotherapy. From the three-month evaluation after radiation therapy, we found a significant reduction in the tumor mass. Conclusions: Surgery remains the treatment of choice for patients with salivary gland malignancies. Definitive radiotherapy can be a treatment modality in inoperable cases or patients who refuse surgery. Although the result is not satisfactory, radiotherapy can still give clinical benefits to patients.

High-grade salivary gland cancer: is surgery followed by radiotherapy an adequate treatment to reach tumor control? Results from a tertiary referral centre focussing on incidence and management of distant metastases

Purpose Salivary Gland cancer (SGC) is a rare and heterogenous group of tumors. Standard therapeutic options achieve high local but poor distant control rates, especially in high-grade SGC. The aim of this monocentric study was to evaluate patterns of recurrence and its treatment options (local ablative vs. systemic) in a homogenously treated patient population with high-grade SGC after surgery and radio(chemo)therapy. Methods Monocentric, retrospective study of patients with newly diagnosed high-grade salivary gland cancer. We retrospectively reviewed clinical reports from 69 patients with high-grade salivary gland cancer in a single-center audit. Survival rates were calculated using the Kaplan–Meier method and prognostic variables were analyzed (univariate analysis: log-rank test; multivariate analysis: Cox regression analysis). Results The median time of follow-up was 31 months. After 5 years, the cumulative overall survival was 65.2%, cumulative incidence of local recurrence was 7.2%, whereas the cumulative incidence of distant metastases was 43.5% after 5 years. 30 of 69 patients developed distant metastases during the time of follow-up, especially patients with adenoid cystic carcinoma, salivary duct carcinoma, adenocarcinoma NOS and acinic cell carcinoma with high-grade transformation. The most common type of therapy therefore was chemotherapy (50%). 85.7% of patients with local ablative therapy of distant metastases show disease progression during follow-up afterwards. Conclusion With surgery and radio-chemotherapy, a high rate of loco-regional control is reached, but over 40% of patients develop distant metastases in the further follow-up which usually present a diffuse pattern involving in a diffuse metastases. Therefore, in the future, intensified interdisciplinary combination therapies even in the first-line treatment in certain subtypes of high-grade SGC should be investigated.