Primary Salivary Gland Carcinomas Research Articles

[Salivary Gland Tumors: Limitations of International Guidelines and Status of the planned AWMF-S3-Guideline].

Primary salivary gland carcinomas are not among the common head and neck tumors. They are characterized by manifold different histological types. Clinically, malignant tumors often cannot be distinguished from benign tumors, so that in these cases malignancy is only established by histopathological diagnosis. These are all reasons why there are relatively few clinical trials on the diagnosis, therapy and follow-up of these tumors. This in turn has the consequence that often only recommendations with limited evidence can be made in clinical guidelines. The most important international guidelines are the National Comprehensive Cancer Network (NCCN) guideline of 2023, the American Society of Clinical Oncology (ASCO) guideline of 2021, the European Society for Medical Oncology (ESMO) guideline of 2022 and still the British National Multidisciplinary guideline of 2016. These 4 international guidelines with their strengths and limitations are presented and commented here. Against this background, the development of a first German S3 clinical guideline on salivary gland tumors is important and expected to be completed in 2023. For the first time in the German guideline program on oncology, benign and malignant tumors are presented together in order to comprehensively do justice to the special features of salivary gland tumors.

Primary salivary gland carcinoma with unusual morphologic features

Primary salivary gland carcinoma with unusual morphologic features

[TRPS1 expression in salivary gland-type breast carcinoma and its clinical application].

Objective: To investigate the expression of TRPS1 in salivary gland-type breast carcinoma and its clinical application. Methods: A total of 30 cases of salivary gland-type breast carcinoma diagnosed from May 2015 to November 2022 at the Department of Pathology of the First Affiliated Hospital of Nanjing Medical University were collected. The expression of TRPS1 was detected by immunohistochemistry and compared with that of GATA3. TRPS1 and GATA3 expression in 24 cases of primary salivary gland carcinoma. Results: There were 10 cases of breast secretory carcinoma, aged 21-61 years (median 53.5 years), with the size ranging from 0.9-2.2 cm (median 1.6 cm), 2 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 2-55 months of follow-up (median 29.5 months, mean 29.7 months). There were 20 cases of breast adenoid cystic carcinoma, aged 36-77 years (median 53.5 years), with the size ranging from 1.2-5.5 cm (median 2.5 cm), 3 of which were accompanied by axillary nodal macrometastasis. All patients were alive after 3-92 months of follow-up (median 22.5 months, mean 31.7 months), and 1 patient had lung metastasis 15 months after surgery. The medium/high expression ratio of TRPS1 in breast secretory carcinoma was 10/10, which was higher than that of GATA3 (7/10). TRPS1 was also positive in the 2 cases with lymph node metastases. The medium/high expression rate of TRPS1 in breast adenoid cystic carcinoma was 20/20, which was significantly higher than that of GATA3 (2/20). TRPS1 was highly expressed in both classic and solid subtypes, while GATA3 was only expressed in a few cases of the classic subtype. TRPS1 was also positive in 3 cases with lymph node metastases and 1 case of the pulmonary metastases. The expression level of TRPS1 was the same in 1 case before and after neoadjuvant chemotherapy. In addition, TRPS1 was positive in parotid secretory carcinoma and adenoid cystic carcinoma. The medium/high expression rate of TRPS1 in parotid secretory carcinoma (6/6) was higher than that of GATA3 (2/6), and the medium/high expression rate of TRPS1 in parotid adenoid cystic carcinoma (17/18) was higher than that of GATA3 (2/18). Conclusions: The expression of TRPS1 is highly sensitive to salivary gland-type breast carcinoma, especially in GATA3-negative solid subtype of adenoid cystic carcinoma, which plays an important role in clinical practice.

Nectin-4 is frequently expressed in primary salivary gland cancer and corresponding lymph node metastases and represents an important treatment-related biomarker

Many locally advanced and metastatic salivary gland carcinomas (SGC) lack therapeutic targets. Enfortumab vedotin, an antibody–drug conjugate binding to Nectin-4, recently gained FDA approval for third-line urothelial carcinoma. Therefore, the aim of this study was to assess the expression of Nectin-4 in primary SGC and corresponding lymph node metastases and to correlate it with clinicopathological data. Immunohistochemical staining for Nectin-4 was performed for patients who had undergone surgery with curative intent for primary SGC of the parotid or submandibular gland in a tertiary referral center between 1990 and 2019. One hundred twenty-two primary SGC and twenty corresponding lymph node metastases were included. Nectin-4 was expressed in 80.3% of primary SGC with a mean Histo(H-)score of 61.2 and in 90.0% of lymph node metastases with a mean H-score of 75.6. A moderate or high Nectin-4 expression was found in 25.9% of salivary duct carcinomas (SaDu) and in 30.7% of adenoid cystic carcinomas (ACC). SaDu patients with a lower T-stage (p = 0.04), no loco-regional lymph node metastases (p = 0.049), no vascular invasion (p = 0.04), and no perineural spread (p = 0.03) showed a significantly higher mean Nectin-4 H-score. There was a statistical tendency towards a more favorable disease-free survival among SaDu patients with a higher Nectin-4 expression (p = 0.09). Nectin-4 is expressed in SGC and therefore represents a potential therapeutic target, especially in entities with a high rate of local recurrence and metastatic spread such as SaDu and ACC.

The protective role of postoperative radiation therapy in low and intermediate grade major salivary gland malignancies: A study of the Canadian Head and Neck Collaborative Research Initiative.

The objective of this study was to examine the utility of postoperative radiation for low and intermediate grade cancers of the parotid and submandibular glands. The authors conducted a retrospective, Canadian-led, international, multi-institutional analysis of a patient cohort with low or intermediate grade salivary gland cancer of the parotid or submandibular gland who were treated from 2010 until 2020 with or without postoperative radiation therapy. A multivariable, marginal Cox proportional hazards regression analysis was performed to quantify the association between locoregional recurrence (LRR) and receipt of postoperative radiation therapy while accounting for patient-level factors and the clustering of patients by institution. In total, 621 patients across 14 tertiary care centers were included in the study; of these, 309 patients (49.8%) received postoperative radiation therapy. Tumor histologies included 182 (29.3%) acinic cell carcinomas, 312 (50.2%) mucoepidermoid carcinomas, and 137 (20.5%) other low or intermediate grade primary salivary gland carcinomas. Kaplan-Meier LRR-free survival at 10years was 89.0% (95% confidence interval [CI], 84.9%-93.3%). In multivariable Cox regression analysis, postoperative radiation therapy was independently associated with a lower hazard of LRR (adjusted hazard ratio, 0.53; 95% CI, 0.29-0.97). The multivariable model estimated that the marginal probability of LRR within 10years was 15.4% without radiation and 8.8% with radiation. The number needed to treat was 16 patients (95% CI, 14-18 patients). Radiation therapy had no benefit in patients who had early stage, low-grade salivary gland cancer without evidence of nodal disease and negative margins. Postoperative radiation therapy may reduce LLR in some low and intermediate grade salivary gland cancers with adverse features, but it had no benefit in patients who had early stage, low-grade salivary gland cancer with negative margins.

Her2 expression can predict the survival of patients with salivary duct carcinoma

Salivary duct carcinoma (SDC) is a high-grade malignant tumor that mainly develops in the salivary glands, and SDC patients have a 5-year survival rate of less than 50%. Thirteen SDC patients (11 male and 2 female, average age 67.2 years) with primary salivary gland carcinoma who received primary treatment in our department from 2005 to 2016. Although markers such as androgen receptors and gross cystic disease fluid protein-15 are effective in diagnosing SDC, there are no effective tumor-specific markers for prognosis prediction. Therefore, we investigated the expressions of human epidermal growth factor receptor 2 (Her2), Ki-67, EGFR, p16, P53 and PD-L1, and examined their prognostic effect. Multivariate analysis showed that high Her2 expression was an exacerbating prognostic factor. In the future, the use of molecular-targeted drugs and immune checkpoint inhibitors for salivary gland malignancies may become more frequent. Her2 expression could be used as a predictor of prognosis.

Intensity-modulated proton and carbon-ion radiation therapy in the management of major salivary gland carcinomas

Primary major salivary gland carcinomas (SGCs) present with diverse histological types that are known to be largely radioresistant with a high tendency to develop distant metastasis (DM). Photon-based radiotherapy (RT) is limited in terms of its therapeutic effect and toxicities. In view of the physical and biological advantages of intensity-modulated proton and/or carbon-ion radiation therapy, we aimed to evaluate the short-term therapeutic effect and toxicities in patients with major SGCs treated with this form of radiation therapy. Between August 2015 and November 2019, a total of 55 consecutive and non-selected major SGC patients who received particle RT at the Shanghai Proton and Heavy Ion Center (SPHIC) were retrospectively analyzed. The 2-year overall survival (OS), progression-free survival (PFS), local-regional recurrence-free survival (LRRFS), and distant metastasis-free survival (DMFS) rates, as well as prognostic factors were analyzed. Additionally, acute and late toxicities were also analyzed. With a median follow-up time of 24 (range, 6-57) months, the 2-year OS, PFS, LRRFS, and DMFS rates were 91.6%, 78.6%, 94.2%, and 83.9%, respectively. At the time of this analysis, four patients had developed local or regional recurrence, and seven additional patients had developed DM. Three patients had died due to disease progression, and another patient with recurrence experienced a late Grade 5 event (hemorrhage) at 9 months after re-irradiation with carbon ion and subsequently died. Otherwise, none of the patients had grade 3 or higher treatment-induced acute or late adverse effects except one who developed grade 3 acute mucositis. Overall, intensity-modulated proton and/or carbon-ion radiation therapy provided satisfactory therapeutic effectiveness in our major SGCs patients with a low incidence of acute and late toxicities.

Incidence and clinical outcome of primary carcinomas of the major salivary glands: 10-year data from a population-based state cancer registry in Germany

PurposeThe aim of this project was to provide an overview of the epidemiology of primary salivary gland carcinomas (SGC) in terms of incidence, distribution of clinicopathological features and survival in one of the largest cancer registries in Europe.MethodsData were collected from patients with SGC of the major salivary glands registered in the population-based state cancer registry (Landeskrebsregister LKR) in North Rhine-Westphalia (NRW), Germany from 01/01/2009 to 12/31/2018. Age standardization of incidence was performed and relative survival estimates were computed by sex, histological group, age group and T-, N-, and M-stage.ResultsA total of 1680 patients were included in this analysis. The most frequent tumor localization was the parotid gland (78%). Adenocarcinoma (not otherwise specified) was the most common tumor entity (18.5%). Most tumors were found in stages T1–T3 (29% T1; 29% T2; 28% T3). The age-standardized incidence rate (ASR) for SGC was 0.65/100,000 and remained stable during the observation period. There was an age-dependent incidence increasing especially from the age 70 years and onwards. The overall 5-year relative survival (RS) for all patients with SGC was 69.2%. RS was 80–95.6% for T1–2 stage tumors, 60.3% for T3, 47.3% for T4 stage, 87.4% for N0 and 51.2% for N1–2, 74.4% for M0 and 44.9% for M1.ConclusionAge-standardized incidence for SGC has been stable for the observed 10-year period. Smaller tumors and those without lymph node or distant metastases had a better RS than more advanced tumors.

CD138 Is Expressed in Different Entities of Salivary Gland Cancer and Their Lymph Node Metastases and Therefore Represents a Potential Therapeutic Target.

Advanced salivary gland carcinomas (SGC) often lack therapeutic options. Agents targeting CD138 have recently shown promising results in clinical trials for multiple myeloma and a preclinical trial for triple-negative breast cancer. Immunohistochemistry for CD138 was performed for all patients who had undergone primary surgery for SGC with curative intent. Findings were validated using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) imaging. Overall, 111 primary SGC and 13 lymph node metastases from salivary duct carcinomas (SaDu) were evaluated. CD138 expression was found in 60% of all SGC with differing expression across entities (p < 0.01). A mean of 25.2% of the tumor cells in mucoepidermoid carcinoma (MuEp) were positive, followed by epithelial-myoepithelial carcinoma (20.9%), acinic cell carcinoma (16.0%), and SaDu (15.2%). High-/intermediate-grade MuEp showed CD138 expression in a mean of 34.8% of tumor cells. For SaDu, lymph node metastases showed CD138 expression in a mean of 31.2% of tumor cells which correlated with CD138 expression in their primaries (p = 0.01; Spearman’s ρ = 0.71). MALDI-MS imaging confirmed the presence of the CD138 protein in SGC. No significant association was found between clinicopathological data, including progression-free survival (p = 0.50) and CD138 expression. CD138 is expressed in the cell membrane of different entities of SGC and SaDu lymph node metastases and therefore represents a potential target for CD138 targeting drugs.

Potential role of hybrid positron emission tomography in pre-operative assessment of primary salivary gland carcinomas.

The added value of hybrid positron emission tomography is increasingly recognised in head and neck cancer. However, its potential role in salivary gland carcinomas has been scarcely investigated. A consecutive cohort of 45 salivary gland carcinoma patients who underwent pre-therapeutic hybrid positron emission tomography and surgical resection was reviewed. This study investigated whether maximum standardised uptake value correlated with tumour phenotype. Tumours of high-grade disease on histology (salivary duct carcinoma, carcinoma ex pleomorphic adenoma) had higher maximum standardised uptake value (Kruskal-Wallis test, p = 0.011) than low-grade tumours (adenoid cystic carcinoma and acinic cell carcinoma). Patients with pathologically confirmed node-positive disease had significantly higher maximum standardised uptake value of the primary tumour than patients with pathologically confirmed node-negative disease (Kruskal-Wallis test, p = 0.012). Maximum standardised uptake value of the primary tumour may guide clinical decision-making in patients with salivary gland carcinomas, as a high maximum standardised uptake value is associated with high-grade tumour histology and the presence of lymph node metastases. Clinicians may consider more aggressive surgery for these patients.

Salivary duct carcinoma- Role of accurate diagnosis for an accurate therapy

Salivary duct carcinoma is an aggressive subtype of primary salivary gland carcinoma with advanced stage at presentation, high rates of metastasis and recurrence. It is most commonly seen in parotid gland of older men with microscopic resemblance to high-grade breast ductal carcinoma. Salivary duct carcinoma mainly affects men over 50 years of age and accounts for 5% to 10% of all salivary gland malignancies. Characteristic histomorphology and immunohistochemical expression of Androgen Receptor (AR) aids the diagnosis of salivary duct carcinoma. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma. Heterologous alterations have been recognized in oncogenes and tumor suppressor genes such as TP53, HRAS, PIK3CA, PTEN, and BRAF as well as AR and HER2. Targeted therapy against these genes may help in broadening treatment options for salivary duct carcinoma. Salivary Duct Carcinoma is one of the most aggressive salivary malignancies with 33% local recurrence and 45% metastasis. We report a case of a 75 years old female patient, who presented with a swelling obliterating the retromandibular groove. FNAC &amp; histopathology confirmed the diagnosis of salivary duct carcinoma.&#x0D;  

Twenty-seven years of primary salivary gland carcinoma in Wales: an analysis of histological subtype and associated risk factors.

Risk factors for salivary gland carcinoma are poorly understood. Although links between background radiation, smoking and obesity have been previously suggested, no studies have so far established any significant results. This study aimed to establish correlations between common environmental and lifestyle risk factors and different subtypes of salivary gland carcinoma. A study of population data in Wales spanning 27 years was conducted; 2 national databases were used to identify 356 cases of primary salivary gland carcinoma over this period. Histological subtype of cancer and geographical location of each case was recorded. Public health data was used to establish radon levels, smoking, obesity and activity levels of populations in each geographical location. A population matched multivariate analysis of variance analysis was performed using histological subtype and risk factor data for each geographical location. A significantly higher incidence of mucoepidermoid cancer in populations with higher background radon levels (p = 0.006), epithelial-myoepithelial cancer in populations with higher smoking levels (p = 0.029) and adenoid cystic cancer in populations with higher obesity levels (p = 0.028) was found. To the authors' knowledge, this is the first study to establish significant links between background radiation, smoking and obesity with different subtypes of salivary gland carcinoma.

Myoepithelial carcinoma of mandible: A rare case with literature review

Primary salivary gland carcinomas of intraosseous origin of the mandible are uncommon neoplasms. Myoepithelial carcinoma (MC) happens to be the rarest. Detailed descriptions of its clinical course are hence not available. Herein, we report a case of MC affecting the mandibular central arch in a bizarre way in a 15-year-old adolescent girl who was treated effectively with definitive radiotherapy (RT) along with concurrent chemotherapy in view of unresectability. To the author's best knowledge, this is the fifth reported case of MC affecting the mandible and the first case to be treated by radical RT. Our study sheds light on the fact that RT can be an effective alternative to surgery where it is not feasible.

Potential biomarkers and signaling pathways associated with the pathogenesis of primary salivary gland carcinoma: a bioinformatics study.

Salivary gland carcinoma (SGC) is rare cancer, constituting 6% of neoplasms in the head and neck area. The most responsible genes and pathways involved in the pathology of this disorder have not been fully understood. We aimed to identify differentially expressed genes (DEGs), the most critical hub genes, transcription factors, signaling pathways, and biological processes (BPs) associated with the pathogenesis of primary SGC. The mRNA dataset GSE153283 in the Gene Expression Omnibus database was re-analyzed for determining DEGs in cancer tissue of patients with primary SGC compared to the adjacent normal tissue (adjusted p-value < 0.001; |Log2 fold change| > 1). A protein interaction map (PIM) was built, and the main modules within the network were identified and focused on the different pathways and BP analyses. The hub genes of PIM were discovered, and their associated gene regulatory network was built to determine the master regulators involved in the pathogenesis of primary SGC. A total of 137 genes were found to be differentially expressed in primary SGC. The most significant pathways and BPs that were deregulated in the primary disease condition were associated with the cell cycle and fibroblast proliferation procedures. TP53, EGF, FN1, NOTCH1, EZH2, COL1A1, SPP1, CDKN2A, WNT5A, PDGFRB, CCNB1, and H2AFX were demonstrated to be the most critical genes linked with the primary SGC. SPIB, FOXM1, and POLR2A significantly regulate all the hub genes. This study illustrated several hub genes and their master regulators that might be appropriate targets for the therapeutic aims of primary SGC.

Outcome of primary pulmonary salivary gland-type carcinoma

Abstract Introduction/Objective Primary pulmonary salivary gland-type carcinomas are rare malignancies that arise from minor salivary gland tissue present within seromucinous submucosal glands within the lower respiratory tract. Due to their rarity (~ &amp;lt;1% of all primary lung malignancies), the epidemiological features and outcome of these malignancies are not well documented. Data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database was analyzed to identify cases of primary pulmonary salivary gland carcinoma. The most common tumor types included mucoepidermoid carcinoma (MEC), adenoid cystic carcinoma (ADCC), and epithelial-myoepithelial carcinoma (EMEC). The tumors were analyzed for overall survival across various epidemiological factors. Methods/Case Report All patients diagnosed with MEC, ADCC, and EMEC with the lung designated as the primary site between the period of 1975 to 2017 were analyzed. We calculated overall survival and disease-specific survival with Kaplan-Meier curves and Cox proportional hazards models using SPSS v25. Results (if a Case Study enter NA) 323 cases of MEC, 284 cases of ADCC, and 6 cases of EMEC diagnosed as primary lung carcinoma were identified. Age distribution analysis of the patients showed a unimodal distribution for both MEC and ADCC with most patients being diagnosed after the age of 40. 54% of MEC patients were male, while 48% of ADCC patients were male. The majority of patients were Caucasians (77% for MEC and 83% for ADCC patients). Both disease-specific and overall survival were worse for patients diagnosed at the age of 60 years or above. Race or sex did not significantly affect patients’ survival. High-grade MEC showed significantly worse prognosis than low or intermediate grade MEC. EMEC cases were too few (n=6) to perform reliable survival analysis, however, the age of diagnosis was higher (45 and above) with a higher incidence among black population (50%). Conclusion Comprehensive review of clinical and epidemiological features of primary salivary gland-type lung carcinoma show that the age of diagnosis and tumor grade are the most significant factor in determining the survival of these patients.

Trophoblast Cell Surface Antigen 2 (Trop-2) Protein is Highly Expressed in Salivary Gland Carcinomas and Represents a Potential Therapeutic Target

Treatment options for unresectable, recurrent or metastatic salivary gland carcinomas (SGC) are scarce. Trophoblast cell surface antigen 2 (Trop-2) is a transmembrane glycoprotein that is involved in a variety of oncogenic cell signaling pathways. Its potential as a target for the antibody–drug conjugate sacituzumab govitecan has already been demonstrated in different tumor entities. The United States Food and Drug Administration approved this antibody–drug conjugate for the treatment of metastatic triple-negative breast cancer. Here, we aimed to investigate Trop-2 protein expression in different entities of SGCs. We retrospectively reviewed the medical records of all patients that underwent surgery for a primary SGC in a tertiary referral center between 1990 and 2014. Immunohistochemical (IHC) staining for Trop-2 was performed and rated as negative, weak, moderate or high using a semiquantitative score. Additionally, representative cases were analyzed using MALDI-mass spectrometry (MS) imaging to confirm the IHC results. The cohort consisted of 114 tumors of the parotid gland (90.4%) and submandibular gland (9.6%). It mainly included mucoepidermoid, salivary duct and adenoid cystic carcinomas. In IHC samples, 44% showed high, 38% moderate and 10% weak expression rates of Trop-2. MALDI-MS imaging confirmed the presence of Trop-2 protein in 80% of the tested tumor samples. This is the first study to demonstrate that several types of SGC express Trop-2 with variable intensity. Since there are currently few systemic treatment options for advanced SGCs, Trop-2 represents a promising target for further clinical studies, for instance, with sacituzumab govitecan.

Surgical treatment of the neck in patients with salivary gland carcinoma.

Elective neck dissection (END) in patients with salivary gland carcinoma is controversial and there are no universally accepted guidelines. Patients were identified from the Danish Head and Neck Cancer Group. Between 2006 and 2015, 259 patients with primary salivary gland carcinoma were treated with END. Variables potentially associated with regional metastases were analyzed using logistic regression. Neck recurrence-free survival was calculated using the Kaplan-Meier method. Occult metastases were found in 36 of the patients treated with END (14%) and were particularly frequent among patients with T3/T4 tumors and high-grade histology tumors. In multivariate analyses, high-grade histology and vascular invasion were associated with occult metastases. We recommend END of levels II and III for patients with high-grade or unknown histological grade tumors, and for T3/T4 tumors. Levels I, II, and III should be included in END in patients with submandibular, sublingual, or minor salivary gland carcinomas.

Therapeutic implications of immune-profiling and EGFR expression in salivary gland carcinoma.

Data relating to the efficacy of immune checkpoint inhibitors (ICI) for salivary gland carcinomas (SGC) is gradually evolving with responses varying among different histotypes. To address these disparities, this retrospective analysis examined the prevalence of recognized biomarkers of response to ICI; namely programmed death-1 (PD-1), programmed death-ligand 1 (PD-L1), combined positive score (CPS), epidermal growth factor receptor (EGFR), and microsatellite instability (MSI) in patients with SGC with an aim to determine any prognostic or survival benefits and stratify the use of ICI in this disease. Of 52 patients with primary SGC eligible for this study, the most common histological types were adenoid cystic carcinoma (n = 17, 33%), salivary duct carcinoma (n = 14, 27%), mucoepidermoid carcinoma (n = 11, 21%), and acinic cell carcinoma (n = 6, 11%). Immunohistochemistry (IHC) was performed using the Ventana Discovery Ultra auto-staining platform for EGFR, PD-1, PD-L1, and mismatch repair (MMR) proteins. CPS ≥1 defined PD-L1 positive cases and log-rank testing was performed to examine the relationship between PD-L1 expression status and disease-free survival (DFS) and overall survival (OS). CPS positivity was seen in 9 (17.3%) patients, none of which were adenoid cystic carcinoma. All 52 (100%) cases expressed retained MMR proteins inferring microsatellite stability (MSS) and EGFR expression was identified in 45 of 52 (86.5%) patients. CPS positivity (score ≥1) was significantly associated with advanced pathological T status (P = .021), advanced pathological N status (P = .006), high histological tumor grade (P = .045), and positive histological margin (P = .023). Patients with PD-L1 positivity in tumor cells did not have an inferior 3-year OS (P = .93). The data from this retrospective study highlighting the uniform microsatellite stability alongside the low prevalence of CPS positivity suggests that only a minority of SGC patients may benefit from ICI therapy alone. The high rates of EGFR expression in SGC may be a target to augment immune checkpoint therapy response.

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

PurposeThis 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.MethodsTwenty-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.ResultsNine 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.ConclusionTreatment-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.

Salivary duct carcinoma: Updates in histology, cytology, molecular biology, and treatment.

Salivary duct carcinoma (SDC) is an aggressive subtype of primary salivary gland carcinoma, often with an advanced stage at presentation and high rates of metastasis and recurrence. It most commonly arises in the parotid gland of older men and microscopically resembles high-grade breast ductal carcinoma. While 50years have lapsed since the first report of this entity, recent intensive studies have shed light on its biologic, genetic, and clinical characteristics. The diagnosis of SDC is aided by the immunohistochemical expression of androgen receptor (AR) coupled with its characteristic histomorphology. Fine-needle aspiration typically reveals cytologic features of high-grade carcinoma, and ancillary studies using cell block material can facilitate the specific diagnosis of SDC. In surgical specimens, certain histologic features are important prognostic factors, including nuclear pleomorphism, mitotic counts, vascular invasion, and the morphology at the invasion front. Several clinical studies have shown promising results using targeted therapy for AR and human epidermal growth factor receptor 2 (HER2), and the latest version of the National Comprehensive Cancer Network guidelines recommends the evaluation of AR and HER2 status before treatment. Recent molecular analyses have revealed multiple heterogeneous alterations in well-known oncogenes and tumor suppressor genes, including TP53, HRAS, PIK3CA, PTEN, and BRAF. Clinical trials of drugs targeting these genes may broaden the treatment options for SDC in the near future.