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

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas J. W. Klein Nulent ◽  
Robert J. J. van Es ◽  
Stefan M. Willems ◽  
Arthur. J. A. T. Braat ◽  
Lot A. Devriese ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Side Effects ◽  
Transmembrane Protein ◽  
Unmet Need ◽  
Salivary Gland Cancer ◽  
Regular Treatment ◽  
Psma Pet ◽  
Pet Ct ◽  
Salivary Gland Carcinomas ◽  
Radiological Response

Abstract 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.

scholarly journals Radiation-induced toxicities and outcomes after radiotherapy are independent of patient age in elderly salivary gland cancer patients: results from a matched-pair analysis of a rare disease

2020 ◽  
Author(s):  
Alexander Rühle ◽  
Sofie Rothhaar ◽  
Erik Haehl ◽  
Tobias Kalckreuth ◽  
Tanja Sprave ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Elderly Patients ◽  
Cancer Patients ◽  
Matched Pair ◽  
Salivary Gland Cancer ◽  
Younger Patients ◽  
Matched Pair Analysis ◽  
Salivary Gland Carcinomas ◽  
Comorbidity Burden ◽  
Pair Analysis

Abstract Purpose This study analyzed survival and toxicity after (chemo)radiotherapy for primary salivary gland cancer patients aged ≥ 65 years and compared these results with younger patients using a matched-pair analysis. Methods Twenty-nine elderly patients with primary salivary gland carcinomas treated with (chemo)radiotherapy from 2008 to 2020 at University of Freiburg Medical Center were analyzed for oncological outcomes and therapy-associated toxicities. Local/locoregional control (LRC), progression-free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method, and the influence of clinical parameters on patient outcomes was assessed. A matched-pair analysis was performed after matching with patients < 65 years. Results Nine patients (31.0%) received definitive (chemo)radiotherapy, and 20 patients (69.0%) were treated in the adjuvant setting. 2-year LRC, PFS and OS ranged at 82.4%, 53.7% and 71.8%, respectively. Smoking (HR 3.980, p = 0.020), reduced performance status (HR 3.735, p = 0.016) and higher comorbidity burden (HR 4.601, p = 0.005) correlated with inferior OS. Using a matched-pair analysis with younger patients, elderly patients exhibited a trend towards reduced OS (HR 3.015, p = 0.065), but not PFS (HR 1.474, p = 0.371) or LRC (HR 1.324, p = 0.633). Acute and chronic grade 3 toxicities occurred in 31.0% and 12.5% of elderly patients, respectively, and the matched-pair analysis revealed no significant differences between age groups regarding treatment-related toxicities. Conclusion Treatment-related toxicities as well as LRC and PFS were comparable for salivary gland cancer patients undergoing radiotherapy. Therefore, concerns for more pronounced toxicities or reduced local/locoregional response rates should not guide treatment decisions in affected elderly patients.

18F-FDG PET/CT Versus Contrast-Enhanced CT for Staging and Prognostic Prediction in Patients With Salivary Gland Carcinomas

2017 ◽  
Vol 42 (3) ◽  
pp. e149-e156 ◽  
Author(s):  
Marn Joon Park ◽  
Jungsu S. Oh ◽  
Jong-Lyel Roh ◽  
Jae Seung Kim ◽  
Jeong Hyun Lee ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Fdg Pet ◽  
Contrast Enhanced Ct ◽  
Contrast Enhanced ◽  
Pet Ct ◽  
Enhanced Ct ◽  
Salivary Gland Carcinomas ◽  
18F Fdg ◽  
Prognostic Prediction ◽  
Fdg Pet Ct

scholarly journals Autophagy and salivary gland cancer: A putative target for salivary gland tumors

Tumor Biology ◽  
2020 ◽  
Vol 42 (12) ◽  
pp. 101042832098056
Author(s):  
Evangelos Koustas ◽  
Panagiotis Sarantis ◽  
Margarita Theodorakidou ◽  
Michalis V Karamouzis ◽  
Stamatios Theocharis
Keyword(s):  
Salivary Gland ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
In Vivo Studies ◽  
Salivary Gland Cancer ◽  
Number Of Patients ◽  
Salivary Gland Carcinomas

Salivary gland carcinomas are a group of heterogeneous tumors of different histological subtypes, presenting relatively low incidence but the entire variable of types. Although novel treatment options for salivary gland carcinomas patients’ outcomes have improved, the treatment of this type of cancer is still not standardized. In addition, a significant number of patients, with a lack of optimal treatment strategies, have reduced survival. In the last two decades, a plethora of evidence pointed to the importance of autophagy, an essential catabolic process of cytoplasmatic component digestion, in cancer. In vitro and in vivo studies highlight the importance of autophagy in salivary gland carcinomas development as a tumor suppressor or promoter mechanism. Despite the potential of autophagy in salivary gland carcinomas development, no therapies are currently available that specifically focus on autophagy modulation in salivary gland carcinomas. In this review, we summarize current knowledge and clinical trials in regard to the interplay between autophagy and the development of salivary gland carcinomas. Autophagy manipulation may be a putative therapeutic strategy for salivary gland carcinomas patients.

Detection of distant metastasis and prognostic prediction of recurrent salivary gland carcinomas using 18 F-FDG PET/CT

Oral Diseases ◽  
2018 ◽  
Vol 24 (6) ◽  
pp. 940-947 ◽  
Author(s):  
Sang Hun Lee ◽  
Jong-Lyel Roh ◽  
Jae Seung Kim ◽  
Jeong Hyun Lee ◽  
Seung-Ho Choi ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Distant Metastasis ◽  
Fdg Pet ◽  
Pet Ct ◽  
Salivary Gland Carcinomas ◽  
Prognostic Prediction ◽  
Fdg Pet Ct

Salivary Gland Cancer: An Update on Present and Emerging Therapies

2013 ◽  
pp. 257-263
Author(s):  
Julie Carlson ◽  
Lisa Licitra ◽  
Laura Locati ◽  
David Raben ◽  
Fredrik Persson ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Radiation Treatment ◽  
Molecular Genetic ◽  
Concurrent Chemotherapy ◽  
Salivary Gland Cancer ◽  
Growth Factor Signaling ◽  
Primary Therapy ◽  
Emerging Therapies ◽  
Salivary Gland Carcinomas ◽  
Postoperative Setting

Malignant salivary gland tumors make up a small proportion of malignancies worldwide, yet vary widely in terms of histology, patterns of spread, and recurrence. A better understanding of this variability will guide appropriate treatment recommendations and lead to improved outcomes. Recent molecular genetic studies have uncovered a translocation-generated gene fusion network in salivary gland carcinomas that can be used for diagnosis, treatment decisions, and development of specific targeted therapies. The gene fusions encode novel fusion oncoproteins that function as transcriptional coactivators, tyrosine kinase receptors, and transcription factors involved in growth-factor signaling and cell-cycle regulation. While surgery currently is the primary therapy for operable tumors, radiation plays an important role in the postoperative setting, as well as in the definitive setting for inoperable lesions. An awareness of the risk factors for tumor recurrence and spread is important for both adjuvant therapy referrals and for radiation treatment planning purposes. Additionally, chemotherapy is being used increasingly in both the concurrent setting as a radiosensitizer, as well as in the palliative setting for metastatic tumors. Future trials investigating concurrent chemotherapy and radiation, as well as the use of targeted agents based on evolving molecular discoveries, will elucidate optimal personalized approaches for this challenging disease.

68Ga/64Cu PSMA Bio-Distribution in Prostate Cancer Patients: Potential Pitfalls for Different Tracers

2019 ◽  
Vol 12 (3) ◽  
pp. 238-246 ◽  
Author(s):  
Ferdinando Calabria ◽  
Robert Pichler ◽  
Mario Leporace ◽  
Johannes Wolfsgruber ◽  
Pierluigi Coscarelli ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
False Positive ◽  
Transmembrane Protein ◽  
Diagnostic Pitfall ◽  
Psma Pet ◽  
Pet Ct ◽  
Resolution Imaging ◽  
Glutamate Carboxypeptidase ◽  
Diagnostic Pitfalls

Background:68Ga-PSMA is a widely useful PET/CT tracer for prostate cancer imaging. Being a transmembrane protein acting as a glutamate carboxypeptidase enzyme, PSMA is highly expressed in prostate cancer cells. PSMA can also be labeled with 64Cu, offering a longer half-life and different resolution imaging. Several studies documented bio-distribution and pitfalls of 68Ga-PSMA as well as of 64Cu- PSMA. No data are reported on differences between these two variants of PSMA. Our aim was to evaluate physiological distribution of these two tracers and to analyze false positive cases.Methods:We examined tracer bio-distribution in prostate cancer patients with negative 68Ga-PSMA PET/CT (n=20) and negative 64Ga-PSMA PET/CT (n=10). A diagnostic pitfall for each tracer was documented.Results:Bio-distribution of both tracers was similar, with some differences due to renal excretion of 68Ga- PSMA and biliary excretion of 64Cu-PSMA. 68Ga-PSMA uptake was observed in sarcoidosis while 64Cu- PSMA uptake was recorded in pneumonitis.Discussion:Both tracers may present similar bio-distribution in the human body, with similar uptake in exocrine glands and high intestinal uptake. Similarly to other tracers, false positive cases cannot be excluded in clinical practice.Conclusion:The knowledge of difference in bio-distribution between two tracers may help in interpretation of PET data. Diagnostic pitfalls can be documented, due to the possibility of PSMA uptake in inflammation. Our results are preliminary to future studies comparing diagnostic accuracies of 68Ga-PSMA and 64Cu-PSMA.

scholarly journals PSMA PET/CT Identifies Intrapatient Variation in Salivary Gland Toxicity From Iodine-131 Therapy

2020 ◽  
Vol 19 ◽  
pp. 153601212093499
Author(s):  
Vineet Mohan ◽  
Wouter V. Vogel ◽  
Gerlof D. Valk ◽  
Jan P. de Boer ◽  
Marnix G. E. H. Lam ◽  
...  
Keyword(s):  
Salivary Gland ◽  
Salivary Glands ◽  
Acinar Cells ◽  
Cell Loss ◽  
Protective Measures ◽  
Positron Emission ◽  
Psma Pet ◽  
Pet Ct ◽  
Iodine 131 ◽  
Further Development

Introduction: Xerostomia is a well-known complication after iodine-131 (131I) therapy for thyroid carcinoma. It is currently insufficiently understood how the dose and biodistribution of 131I relates to salivary gland toxicity, and whether this is consistent for all salivary glands within a single patient. Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) was recently introduced as a new tool to evaluate the relative loss of vital acinar cells in individual salivary glands. We aimed to assess gland-specific salivary gland toxicity after 131I-therapy using PSMA PET/CT. Methods: Five patients with differentiated thyroid cancer underwent [68Ga]Ga-PSMA-11 PET/CT to evaluate their eligibility for peptide radioligand therapy with [177Lu]Lu-PSMA-617. Uptake patterns in salivary glands were evaluated visually and quantitatively as an indicator of vital acinar cell loss after prior 131I-therapy. Results: Four of 5 patients demonstrated significant lowered uptake in at least one salivary gland, after receiving at least 2 131I-treatments. Asymmetric loss of vital acinar cells occurred by gland type (parotid/submandibular) and location (right/left). The other salivary glands in these patients and all salivary glands in the fifth patient showed normal uptake, demonstrating high intrapatient and interpatient variability. Conclusions: 131I-therapy can induce salivary gland toxicity with high inter- but also high intrapatient variation among separate gland locations, which can be assessed with PSMA PET/CT. This new technique offers potential to guide further development and evaluation of protective measures in patients receiving 131I-therapy.

scholarly journals PSMA radioligand therapy for solid tumors other than prostate cancer: background, opportunities, challenges, and first clinical reports

2021 ◽  
Author(s):  
M. J. M. Uijen ◽  
Y. H. W. Derks ◽  
R. I. J. Merkx ◽  
M. G. M. Schilham ◽  
J. Roosen ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Patients ◽  
Current Knowledge ◽  
Salivary Gland Cancer ◽  
Clinical Implementation ◽  
Radioligand Therapy ◽  
Psma Pet ◽  
Pet Ct ◽  
Specific Membrane ◽  
Psma Expression

AbstractIn the past decade, a growing body of literature has reported promising results for prostate-specific membrane antigen (PSMA)-targeted radionuclide imaging and therapy in prostate cancer. First clinical studies evaluating the efficacy of [177Lu]Lu-PSMA radioligand therapy (PSMA-RLT) demonstrated favorable results in prostate cancer patients. [177Lu]Lu-PSMA is generally well tolerated due to its limited side effects. While PSMA is highly overexpressed in prostate cancer cells, varying degrees of PSMA expression have been reported in other malignancies as well, particularly in the tumor-associated neovasculature. Hence, it is anticipated that PSMA-RLT could be explored for other solid cancers. Here, we describe the current knowledge of PSMA expression in other solid cancers and define a perspective towards broader clinical implementation of PSMA-RLT. This review focuses specifically on salivary gland cancer, glioblastoma, thyroid cancer, renal cell carcinoma, hepatocellular carcinoma, lung cancer, and breast cancer. An overview of the (pre)clinical data on PSMA immunohistochemistry and PSMA PET/CT imaging is provided and summarized. Furthermore, the first clinical reports of non-prostate cancer patients treated with PSMA-RLT are described.

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